Inflammation and loss of connective tissues supporting or surrounding the teeth. This may involve any part of the PERIODONTIUM. Periodontitis is currently classified by disease progression (CHRONIC PERIODONTITIS; AGGRESSIVE PERIODONTITIS) instead of age of onset. (From 1999 International Workshop for a Classification of Periodontal Diseases and Conditions, American Academy of Periodontology)
CD4-positive T cells that inhibit immunopathology or autoimmune disease in vivo. They inhibit the immune response by influencing the activity of other cell types. Regulatory T-cells include naturally occurring CD4+CD25+ cells, IL-10 secreting Tr1 cells, and Th3 cells.
A subclass of winged helix DNA-binding proteins that share homology with their founding member fork head protein, Drosophila.
All of the divisions of the natural sciences dealing with the various aspects of the phenomena of life and vital processes. The concept includes anatomy and physiology, biochemistry and biophysics, and the biology of animals, plants, and microorganisms. It should be differentiated from BIOLOGY, one of its subdivisions, concerned specifically with the origin and life processes of living organisms.
Chronic inflammation and loss of PERIODONTIUM that is associated with the amount of DENTAL PLAQUE or DENTAL CALCULUS present. Chronic periodontitis occurs mostly in adults and was called adult periodontitis, but this disease can appear in young people.
A low affinity interleukin-2 receptor subunit that combines with the INTERLEUKIN-2 RECEPTOR BETA SUBUNIT and the INTERLEUKIN RECEPTOR COMMON GAMMA-CHAIN to form a high affinity receptor for INTERLEUKIN-2.
Inflammation and loss of PERIODONTIUM that is characterized by rapid attachment loss and bone destruction in the presence of little local factors such as DENTAL PLAQUE and DENTAL CALCULUS. This highly destructive form of periodontitis often occurs in young people and was called early-onset periodontitis, but this disease also appears in old people.
This enzyme is a lymphoid-specific src family tyrosine kinase that is critical for T-cell development and activation. Lck is associated with the cytoplasmic domains of CD4, CD8 and the beta-chain of the IL-2 receptor, and is thought to be involved in the earliest steps of TCR-mediated T-cell activation.
A protein tyrosine kinase that is required for T-CELL development and T-CELL ANTIGEN RECEPTOR function.
A conserved AMINO ACID SEQUENCE located in the intracellular domains of a family of transmembrane proteins involved in various IMMUNE RESPONSES. The CONSENSUS SEQUENCE of this motif is YXXL(or I)X(6-8)YXXL(or I) (where X denotes any amino acid). When phosphorylated ITAM motifs provide docking sites for PROTEIN TYROSINE KINASES of the Syk family thus forming signaling complexes which lead to activation of immune responses.
A non-essential amino acid. In animals it is synthesized from PHENYLALANINE. It is also the precursor of EPINEPHRINE; THYROID HORMONES; and melanin.
The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.
Protein kinases that catalyze the PHOSPHORYLATION of TYROSINE residues in proteins with ATP or other nucleotides as phosphate donors.
The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.
The biochemical and electrophysiological interactions between the NERVOUS SYSTEM and IMMUNE SYSTEM.
Interventions to provide care prior to, during, and immediately after surgery.
A medical specialty concerned with the study of the structures, functions, and diseases of the nervous system.
A group of pathological conditions characterized by sudden, non-convulsive loss of neurological function due to BRAIN ISCHEMIA or INTRACRANIAL HEMORRHAGES. Stroke is classified by the type of tissue NECROSIS, such as the anatomic location, vasculature involved, etiology, age of the affected individual, and hemorrhagic vs. non-hemorrhagic nature. (From Adams et al., Principles of Neurology, 6th ed, pp777-810)
A specialty concerned with the study of anesthetics and anesthesia.
A thickening and loss of elasticity of the walls of ARTERIES that occurs with formation of ATHEROSCLEROTIC PLAQUES within the ARTERIAL INTIMA.
A class of protein components which can be found in several lipoproteins including HIGH-DENSITY LIPOPROTEINS; VERY-LOW-DENSITY LIPOPROTEINS; and CHYLOMICRONS. Synthesized in most organs, Apo E is important in the global transport of lipids and cholesterol throughout the body. Apo E is also a ligand for LDL receptors (RECEPTORS, LDL) that mediates the binding, internalization, and catabolism of lipoprotein particles in cells. There are several allelic isoforms (such as E2, E3, and E4). Deficiency or defects in Apo E are causes of HYPERLIPOPROTEINEMIA TYPE III.
Thickening and loss of elasticity of the walls of ARTERIES of all sizes. There are many forms classified by the types of lesions and arteries involved, such as ATHEROSCLEROSIS with fatty lesions in the ARTERIAL INTIMA of medium and large muscular arteries.
Common occlusive arterial disease which is caused by ATHEROSCLEROSIS. It is characterized by lesions in the innermost layer (ARTERIAL INTIMA) of arteries including the AORTA and its branches to the extremities. Risk factors include smoking, HYPERLIPIDEMIA, and HYPERTENSION.
White blood cells formed in the body's lymphoid tissue. The nucleus is round or ovoid with coarse, irregularly clumped chromatin while the cytoplasm is typically pale blue with azurophilic (if any) granules. Most lymphocytes can be classified as either T or B (with subpopulations of each), or NATURAL KILLER CELLS.
Immunosuppression by reduction of circulating lymphocytes or by T-cell depletion of bone marrow. The former may be accomplished in vivo by thoracic duct drainage or administration of antilymphocyte serum. The latter is performed ex vivo on bone marrow before its transplantation.
Morphologic alteration of small B LYMPHOCYTES or T LYMPHOCYTES in culture into large blast-like cells able to synthesize DNA and RNA and to divide mitotically. It is induced by INTERLEUKINS; MITOGENS such as PHYTOHEMAGGLUTININS, and by specific ANTIGENS. It may also occur in vivo as in GRAFT REJECTION.
The specific failure of a normally responsive individual to make an immune response to a known antigen. It results from previous contact with the antigen by an immunologically immature individual (fetus or neonate) or by an adult exposed to extreme high-dose or low-dose antigen, or by exposure to radiation, antimetabolites, antilymphocytic serum, etc.
Messages between computer users via COMPUTER COMMUNICATION NETWORKS. This feature duplicates most of the features of paper mail, such as forwarding, multiple copies, and attachments of images and other file types, but with a speed advantage. The term also refers to an individual message sent in this way.
A publication issued at stated, more or less regular, intervals.
"The business or profession of the commercial production and issuance of literature" (Webster's 3d). It includes the publisher, publication processes, editing and editors. Production may be by conventional printing methods or by electronic publishing.
Critical and exhaustive investigation or experimentation, having for its aim the discovery of new facts and their correct interpretation, the revision of accepted conclusions, theories, or laws in the light of newly discovered facts, or the practical application of such new or revised conclusions, theories, or laws. (Webster, 3d ed)
The profession of writing. Also the identity of the writer as the creator of a literary production.
The use of statistical methods in the analysis of a body of literature to reveal the historical development of subject fields and patterns of authorship, publication, and use. Formerly called statistical bibliography. (from The ALA Glossary of Library and Information Science, 1983)
The guidelines and policy statements set forth by the editor(s) or editorial board of a publication.
CXCR receptors with specificity for CXCL12 CHEMOKINE. The receptors may play a role in HEMATOPOIESIS regulation and can also function as coreceptors for the HUMAN IMMUNODEFICIENCY VIRUS.
An anti-inflammatory 9-fluoro-glucocorticoid.
A group of CORTICOSTEROIDS that affect carbohydrate metabolism (GLUCONEOGENESIS, liver glycogen deposition, elevation of BLOOD SUGAR), inhibit ADRENOCORTICOTROPIC HORMONE secretion, and possess pronounced anti-inflammatory activity. They also play a role in fat and protein metabolism, maintenance of arterial blood pressure, alteration of the connective tissue response to injury, reduction in the number of circulating lymphocytes, and functioning of the central nervous system.
Reduction in the number of lymphocytes.
Cytoplasmic proteins that specifically bind glucocorticoids and mediate their cellular effects. The glucocorticoid receptor-glucocorticoid complex acts in the nucleus to induce transcription of DNA. Glucocorticoids were named for their actions on blood glucose concentration, but they have equally important effects on protein and fat metabolism. Cortisol is the most important example.
Stress wherein emotional factors predominate.
The unfavorable effect of environmental factors (stressors) on the physiological functions of an organism. Prolonged unresolved physiological stress can affect HOMEOSTASIS of the organism, and may lead to damaging or pathological conditions.
A subspecialty of internal medicine concerned with the study of the RESPIRATORY SYSTEM. It is especially concerned with diagnosis and treatment of diseases and defects of the lungs and bronchial tree.
Test for tissue antigen using either a direct method, by conjugation of antibody with fluorescent dye (FLUORESCENT ANTIBODY TECHNIQUE, DIRECT) or an indirect method, by formation of antigen-antibody complex which is then labeled with fluorescein-conjugated anti-immunoglobulin antibody (FLUORESCENT ANTIBODY TECHNIQUE, INDIRECT). The tissue is then examined by fluorescence microscopy.
Measurement of volume of air inhaled or exhaled by the lung.
A dye obtained from the heartwood of logwood (Haematoxylon campechianum Linn., Leguminosae) used as a stain in microscopy and in the manufacture of ink.
Either of the pair of organs occupying the cavity of the thorax that effect the aeration of the blood.

Alternative polyadenylation events contribute to the induction of NF-ATc in effector T cells. (1/7255)

The transcription factor NF-ATc is synthesized in three prominent isoforms. These differ in the length of their C terminal peptides and mode of synthesis. Due to a switch from the use of a 3' polyA site to a more proximal polyA site, NF-ATc expression switches from the synthesis of the two longer isoforms in naive T cells to that of short isoform A in T effector cells. The relative low binding affinity of cleavage stimulation factor CstF-64 to the proximal polyA site seems to contribute to its neglect in naive T cells. These alternative polyadenylation events ensure the rapid accumulation of high concentrations of NF-ATc necessary to exceed critical threshold levels of NF-ATc for gene induction in effector T cells.  (+info)

Development of CD8+ effector T cells is differentially regulated by IL-18 and IL-12. (2/7255)

We investigated the effects of IL-18 on the development of CD8+ effector T cells in DBA/2 anti-BDF1 whole spleen cell MLC and compared the results with those of IL-12. Addition of IL-18 to the MLC resulted in a twofold increase in CD8/CD4 ratios compared with the control cultures when cells were expanded in IL-2-containing medium following MLC. Purified CD8+ T cells recovered from the IL-18-stimulated MLC produced 20- to 30-fold more IFN-gamma after secondary stimulation with C57BL/6 spleen cells or anti-CD3 mAb, and exhibited strong allospecific CTL activity. Neither IL-18 nor IL-18-supplemented culture supernatants from DBA/2 anti-BDF1 MLC induced type I CD8+ effector T cells when purified CD8+ T cells were used as responder cells in primary MLC. Furthermore, CD4+ T cell depletion from the responder cells abrogated the IL-18-induced increase in secondary IFN-gamma production by CD8+ T cells, suggesting that IL-18-induced type I effector CD8+ T cell development was CD4+ T cell dependent. In marked contrast, adding IL-12 to primary MLC decreased CD8/CD4 ratios by 50% and suppressed secondary IFN-gamma production and CTL activity by CD8+ T cells regardless of concentration, whereas Th1 development was promoted by IL-12. Moreover, both IL-12 and IL-18 efficiently induced type I CD8+ effector T cells in C57BL/6 anti-BDF1 MLC. These findings show that IL-18 plays an important role in the generation of type I CD8+ effector T cells, and further suggest that functional maturation of CD8+ T cells is differentially regulated by IL-18 and IL-12.  (+info)

Inflammatory cytokines provide a third signal for activation of naive CD4+ and CD8+ T cells. (3/7255)

The effects of inflammatory cytokines on naive T cells have been studied using MHC protein/peptide complexes on microspheres, thus avoiding the use of APCs whose functions may be affected by the cytokines. IL-1, but not IL-12, increased proliferation of CD4+ T cells in response to Ag and IL-2, which is consistent with effects on in vivo priming of CD4+ cells. In contrast, proliferation of CD8+ T cells to Ag and IL-2 required IL-12, and IL-12 replaced adjuvant in stimulating an in vivo response to peptide. These results support a model in which distinct inflammatory cytokines act directly on naive CD4+ and CD8+ T cells to provide a third signal, along with Ag and IL-2, to optimally activate differentiation and clonal expansion.  (+info)

Thymus and autoimmunity: production of CD25+CD4+ naturally anergic and suppressive T cells as a key function of the thymus in maintaining immunologic self-tolerance. (4/7255)

This study shows that the normal thymus produces immunoregulatory CD25+4+8- thymocytes capable of controlling self-reactive T cells. Transfer of thymocyte suspensions depleted of CD25+4+8- thymocytes, which constitute approximately 5% of steroid-resistant mature CD4+8- thymocytes in normal naive mice, produces various autoimmune diseases in syngeneic athymic nude mice. These CD25+4+8- thymocytes are nonproliferative (anergic) to TCR stimulation in vitro, but potently suppress the proliferation of other CD4+8- or CD4-8+ thymocytes; breakage of their anergic state in vitro by high doses of IL-2 or anti-CD28 Ab simultaneously abrogates their suppressive activity; and transfer of such suppression-abrogated thymocyte suspensions produces autoimmune disease in nude mice. These immunoregulatory CD25+4+8- thymocytes/T cells are functionally distinct from activated CD25+4+ T cells derived from CD25-4+ thymocytes/T cells in that the latter scarcely exhibits suppressive activity in vitro, although both CD25+4+ populations express a similar profile of cell surface markers. Furthermore, the CD25+4+8- thymocytes appear to acquire their anergic and suppressive property through the thymic selection process, since TCR transgenic mice develop similar anergic/suppressive CD25+4+8- thymocytes and CD25+4+ T cells that predominantly express TCRs utilizing endogenous alpha-chains, but RAG-2-deficient TCR transgenic mice do not. These results taken together indicate that anergic/suppressive CD25+4+8- thymocytes and peripheral T cells in normal naive mice may constitute a common T cell lineage functionally and developmentally distinct from other T cells, and that production of this unique immunoregulatory T cell population can be another key function of the thymus in maintaining immunologic self-tolerance.  (+info)

Decreased IL-12 production underlies the decreased ability of male lymph node cells to induce experimental autoimmune encephalomyelitis. (5/7255)

Myelin basic protein (MBP)-specific T lymphocytes from male SJL mice were shown to be less encephalitogenic than MBP-specific T lymphocytes from females. Mechanisms underlying this gender difference in the induction phase of EAE were examined. Following immunization with MBP, draining lymph nodes contained fewer cells, and Ag-specific proliferative responses were decreased in males as compared with females. These gender differences in the proliferative response were not unique to MBP-specific responses since they were also observed after immunization with hen eggwhite lysozyme. Short-term MBP-specific T cell lines derived from females and males mapped with identical specificity, indicating no defect in the ability of male APCs to process Ag. Interestingly, IL-12 and IFN-gamma production was decreased following Ag-specific stimulation of draining lymph node cells (LNC) from males as compared with females, but IL-10 and IL-4 were no different. While male-derived LNCs were less encephalitogenic than female derived LNCs, cotransfer and coculture of male LNCs with female LNCs demonstrated that male LNCs were not immunosuppressive. Administration of IL-12 to LNCs from male mice enhanced encephalitogenicity. These data indicate that deficient endogenous IL-12 production within draining LNCs of male SJL mice is central to gender differences in the induction phase of experimental autoimmune encephalomyelitis.  (+info)

Emergence of regulatory CD4+ T cell response to repetitive stimulation with antigen-presenting cells in vitro: implications in designing antigen-presenting cell-based tumor vaccines. (6/7255)

Because APCs play a crucial role in the generation of T cell-mediated immune responses, numerous clinical trials with APC-based vaccines have been initiated in different types of human cancers. Encouraging results have emerged from some of these initial studies. Thus far, APC-based vaccinations usually include multiple rounds of immunization. With this approach, although we and others have detected induction of Ag-specific CTL responses in vaccinated patients after stimulation with the same APC-based immunogen, in vitro we also find that repetitive in vitro stimulation with Ag-loaded APC can, at times, lead to the emergence of noncytolytic CD4+ T cells exhibiting the characteristic phenotype of Th2 cells. These noncytolytic CD4+ T cells synthesize large quantities of type 2 cytokines such as IL-4 and IL-10 on stimulation with the autologous APC or tumor cells in an MHC class II-restricted manner. Further, these CD4+ T cells and a cell-free supernatant factor block the activation of fresh T lymphocytes. The supernatant factor also exhibits a marked inhibitory effect on the expression of the costimulatory molecules, CD80 and CD86, by APC. The inhibitory effect of the supernatant factor can be abrogated by neutralizing IL-10 in the supernatant. These observations therefore have implications in the APC-based tumor vaccine protocol design.  (+info)

Regulation of apoptosis in mature alphabeta+CD4-CD8- antigen-specific suppressor T cell clones. (7/7255)

The regulation of apoptosis in mature CD4+ or CD8+ alphabeta+ T cells has been well studied. How the survival and death is regulated in peripheral CD4-CD8- (double negative, DN) alphabeta+ T cells remains unknown. Recent studies suggest that peripheral DN T cells may play an important role in the regulation of the immune responses mediated by CD4+ or CD8+ T cells. Here, we used immunosuppressive DN T cell clones to elucidate the mechanisms involved in the regulation of death and survival of alphabeta+ DN T cells. The DN T cell clones were generated from the spleen cells of 2C transgenic mice, which express the transgenic TCR specific for Ld and permanently accepted Ld+ skin allografts after pretransplant infusion of Ld+ lymphocytes. We report that 1) the mature DN T cells are highly resistant to TCR cross-linking-induced apoptosis in the presence of exogenous IL-4; 2) Fas/Fas-ligand and TNF-alpha/TNFR pathways do not play an apparent role in regulating apoptosis in DN T cells; 3) the DN T cells constitutively express a high level of Bcl-xL, but not Bcl-2; 4) both Bcl-xL and Bcl-2 are up-regulated following TCR-cross-linking; and 5) IL-4 stimulation significantly up-regulates Bcl-xL and c-Jun expression and leads to mitogen-activated protein kinase phosphorylation in DN T cells, which may contribute to the resistance to apoptosis in these T cells. Taken together, these results provide us with an insight into how mature DN T cells resist activation-induced apoptosis to provide a long-term suppressor function in vivo.  (+info)

Regulation of the mucosal immune response. (8/7255)

Infectious diseases continue to exact an extensive toll on populations living closest to the equatorial regions of the globe. A substantial proportion of these infections gain access to the host via the mucosal tissues. Thus, the development of new vaccines that enhance mucosal immunity is considered to be of paramount importance in order to prevent or limit the impact of these infections. Mucosal immune responses must discriminate between commensal flora within the lumen and potential pathogens. These responses are highly adapted to induce protection without excessive amounts of inflammation. The balances that regulate mucosal immune and inflammatory responses have to be understood if effective mucosal immunity is to be induced through local immunization. This review will summarize some of the unique properties of mucosal immune responses and focus on recent advances that have significantly influenced our understanding of the regulation of immune and inflammatory responses following infection.  (+info)

TY - JOUR. T1 - In Vitro Induction of Human Regulatory T Cells Using Conditions of Low Tryptophan Plus Kynurenines. AU - Hippen, K. L.. AU - OConnor, R. S.. AU - Lemire, A. M.. AU - Saha, A.. AU - Hanse, E. A.. AU - Tennis, N. C.. AU - Merkel, S. C.. AU - Kelekar, A.. AU - Riley, J. L.. AU - Levine, B. L.. AU - June, C. H.. AU - Turka, L. A.. AU - Kean, L. S.. AU - MacMillan, M. L.. AU - Miller, J. S.. AU - Wagner, J. E.. AU - Munn, D. H.. AU - Blazar, B. R.. PY - 2017/12. Y1 - 2017/12. N2 - Thymic regulatory T cells (tTregs) and induced regulatory T cells (iTregs) suppress murine acute graft-versus-host disease (GVHD). Previously, we demonstrated that the plasmacytoid dendritic cell indoleamine 2,3-dioxygenase (IDO) fosters the in vitro development of human iTregs via tryptophan depletion and kynurenine (Kyn) metabolites. We now show that stimulation of naïve CD4+ T cells in low tryptophan (low Trp) plus Kyn supports human iTreg generation. In vitro, low Trp + Kyn iTregs and tTregs potently ...
The atheroprotective effect paralleled an induction of Treg suppression of apoB-100-specific effector T cells and an increase in IL-10+ CD4+ T cells. Therefore, our data suggest that nasal immunization with p210-CTB protects against atherosclerosis by inducing antigen-specific, IL-10+ regulatory Tr1 cells. It is unlikely that atheroprotection involved the immunosuppressive cytokine TGF-β because nasal immunization with p210-CTB also reduced atherosclerosis in mice lacking a functional TGF-β receptor on T cells.. Antigen-specific as well as antigen-independent effects have been reported in studies of Treg.25 Several studies of autoimmune diseases support the regulation model according to which Treg suppresses conventional effector T cells with the same antigen specificity. Other investigators report that Treg exerts major effects on antigen-presenting cells in an antigen-independent manner. Our data clearly show that antigen-specific atheroprotection was paralleled by inhibition of ...
CD4+Foxp3+ regulatory T cells (Treg)s are essential for the prevention of autoimmunity. Treg lineage commitment requires T cell receptor (TCR) interactions that induce expression of foxp3, whose protein product enforces Treg fate. Treg homeostasis is critical for self-tolerance and is achieved through both Treg generation and maintenance. Treg maintenance occurs in part through a process of self-renewing cell division of existing Tregs. This self-renewing Treg division has been shown to be TCR dependent. Despite the crucial role of the TCR in Treg generation and maintenance, neither the specific signaling pathways that control Treg generation nor the nature of the TCR signals required for their division in the periphery are well understood. Here, we demonstrated that dendritic cells (DC)s coordinate Treg division in vitro. DCs elicit interleukin-2 (IL-2) production from conventional CD4+ T cells (Tconv)s in a major histocompatibility complex class II (MHCII)-dependent fashion. Tconv-derived IL-2
The data presented here provide new insight into the biology of regulatory T cells within the context of a human autoimmune disease. CD4+CD25high T cells isolated from patients with active RA, although still anergic, show compromised function as demonstrated by their inability to regulate proinflammatory cytokines released by effector T cells and monocytes. After Infliximab treatment, regulatory T cell-mediated suppression was restored to the level found in healthy individuals, whereas only a partial restoration was seen in regulatory T cells isolated from patients responding to methotrexate. Although it is well documented that Infliximab blocks both soluble and transmembrane TNFα, resulting in a strong inhibition of other proinflammatory cytokines, there is no unanimity about the effects of methotrexate on cytokine production in RA (21, 22). If proinflammatory cytokines are not efficiently suppressed in methotrexate-treated patients, this could have a deleterious effect on the function of ...
Description of disease T-suppressor cell. Treatment T-suppressor cell. Symptoms and causes T-suppressor cell Prophylaxis T-suppressor cell
Human regulatory T cells (Treg) have been variously defined as CD4(+)CD25(+), CD4(+)CD25(high) or CD4(+)CD25(high)FOXP3(+) cells which are responsible for maintaining peripheral tolerance. Their isolation from human peripheral blood or tissues depends on the expression level of CD25(IL-2Ralpha) - a surface marker which is also expressed on activated effector helper T cells. CD39, a cell surface associated ectonucleotidase, can be used to purify Treg with strong suppressor functions. The CD4(+)CD39(+) T cells catalyze cleavage of adenosine triphosphate (ATP) to adenosine monophosphate (AMP), which is then further cleaved to adenosine. CD4(+)CD39(+) T cells largely overlap with CD4(+)CD25(high)FOXP3(+) but not CD4(+)CD25(+) T cell subset, and mediate equally potent immune suppression. Thus, CD39 surface marker can be successfully used for routine isolation of functionally-active human Treg from the peripheral blood of healthy donors or patients with cancer for studies of their role in health and disease.
Paterson AM, Lovitch SB, Sage PT, Juneja VR, Lee Y, Trombley JD, Arancibia-Cárcamo CV, Sobel RA, Rudensky AY, Kuchroo VK, et al. Deletion of CTLA-4 on regulatory T cells during adulthood leads to resistance to autoimmunity. J Exp Med. 2015.
Regulatory T cells curb unwanted immune responses and regulate responses to microflora and it is now clear that regulatory T cells play an important role in a number of chronic inflammatory diseases of the gut. First, regulatory T cells are crucial in controlling immune responses to gastric autoantigens and thus preventing autoimmune gastritis and pernicious anemia. Second, regulatory T cells may modulate the response to Helicobacter pylori, thus affecting the ability of the immune system to clear the pathogen and mediate damage to the gastric mucosa. Finally, regulatory T cells play an important role in preventing damaging inflammatory responses to commensal organisms in the lower gut, thus guarding against inflammatory bowel diseases. In the present review, we examine the actions of regulatory T cells in the gut and conclude that further understanding of regulatory T cell biology may lead to new therapeutic approaches to chronic gastrointestinal disease ...
The mechanism of LN-specific, Ag-specific Treg enrichment might depend on factors regulating T cell homing to LN, encounter with self-Ag, and their retention in the LN. Homing of naive T cells and Treg to normal LN are known to involve CD62L, CCR7, and the chemokines CCL19 and CCL21 (15). Autoimmune diseases occur in mice deficient in CD62L or CCR7 (16, 17), for which we can now add a potential explanation: the loss of DS-Treg enrichment in regional LN. Treg retention may result from up-regulation of CD69 on Ag-specific Treg that temporarily sequester sphingosine 1-phosphate receptor type 1, which is required for T cell egress from LN (18). Additional mechanisms may involve Treg response to antiapoptotic and/or cellular proliferation signals (19). Constrained by T cell homeostatic mechanisms (20), the number or activity of DS-Treg in the regional LN would be maintained at a threshold 15- to 50-fold greater than those in the nondraining LN.. Additional mechanisms participate in Ag-specific Treg ...
Spellman, C W. and Daynes, R A., Properties of ultraviolet light-induced suppressor lymphocytes within a syngeneic tumor system. (1978). Subject Strain Bibliography 1978. 1859 ...
TY - JOUR. T1 - Altered homeostasis and development of regulatory T cell subsets represent an IL-2R-dependent risk for diabetes in NOD mice. AU - Dwyer, Connor J.. AU - Bayer, Allison L. AU - Fotino, Carmen. AU - Yu, Liping. AU - Cabello-Kindelan, Cecilia. AU - Ward, Natasha C.. AU - Toomer, Kevin H.. AU - Chen, Zhibin. AU - Malek, Thomas. PY - 2017/12/19. Y1 - 2017/12/19. N2 - The cytokine interleukin-2 (IL-2) is critical for the functions of regulatory T cells (Tregs). The contribution of polymorphisms in the gene encoding the IL-2 receptor subunit (IL2RA), which are associated with type 1 diabetes, is difficult to determine because autoimmunity depends on variations in multiple genes, where the contribution of any one gene product is small. We investigated the mechanisms whereby a modest reduction in IL-2R signaling selectively in T lymphocytes influenced the development of diabetes in the NOD mouse model. The sensitivity of IL-2R signaling was reduced by about two- to threefold in Tregs from ...
We used a defined IL-2/αIL-2 complex that directs IL-2 to stimulate only intermediate-affinity IL-2 receptor (CD122/132) to promote tumor rejection and avoid regulatory T cell (Treg) expansion. However, it is unknown if IL-2/αIL-2 alters Treg function, as Tregs also express CD122/132. After challenge with ID8agg ovarian cancer (OC) cells, IL-2/αIL-2 greatly reduced tumor burden, and increased IFN-γ, TNF-α, CD44, and CD25 in CD4+ non-Tregs and CD8+ T cells, as expected. IL-2/αIL-2 was clinically effective, yet it lowered the ascites CD8+/FoxP3+ Treg ratio and increased per cell FoxP3 levels in Tregs, suggesting a change in Treg function. IL-2/αIL-2 decreased the ratio of CD62L+ central Tregs to CD44+ effector Tregs in ID8agg ascites, indicating modulation of Treg differentiation. Surprisingly, ascites Tregs produced IFN-γ, IL-2, and TNF-α in control-treated OC mice, which was abolished by IL-2/αIL-2, suggesting further alteration of Treg differentiation and function. CD25 (high-affinity ...
A paradigm shift in immunology has been the recent discovery of regulatory T cells (T reg cells), of which CD4(+)Foxp3(+) cells are proven as essential to self-tolerance. Using transgenic B6.Foxp3(hCD2) mice to isolate and ablate Foxp3(+) T reg cells with an anti-hCD2 antibody, we show for the first time that CD4(+)Foxp3(+) cells are crucial for infectious tolerance induced by nonablative anti-T cell antibodies. In tolerant animals, Foxp3(+) T reg cells are constantly required to suppress effector T cells still capable of causing tissue damage. Tolerated tissue contains T cells that are capable of rejecting it, but are prevented from doing so by therapeutically induced Foxp3(+) T reg cells. Finally, Foxp3(+) cells have been confirmed as the critical missing link through which infectious tolerance operates in vivo. Peripherally induced Foxp3(+) cells sustain tolerance by converting naive T cells into the next generation of Foxp3(+) cells. Empowering Foxp3(+) regulatory T cells in vivo offers a tractable
Kakita, N., Kanto, T., Itose, I., Kuroda, S., Inoue, M., Matsubara, T., Higashitani, K., Miyazaki, M., Sakakibara, M., Hiramatsu, N., Takehara, T., Kasahara, A. and Hayashi, N. (2012), Comparative analyses of regulatory T cell subsets in patients with hepatocellular carcinoma: A crucial role of CD25−FOXP3− T cells. Int. J. Cancer, 131: 2573-2583. doi: 10.1002/ijc.27535 ...
The TF Foxp3 is a hallmark of Treg cells; however, Foxp3 is not sufficient to control the Treg program alone, and other TFs are important in this regard. This study demonstrates the fundamental role of Bcl11b in regulating the Treg signature program while repressing the innate lineage programs in mouse Treg cells. In the absence of Bcl11b, Treg cells were unable to exert their suppression function, which led to the inability to control multiorgan inflammation. Even when isolated from Bcl11b/Treg KO mosaic female mice, in the absence of inflammation, Bcl11b KO Treg cells failed to control CD45Rbhi CD4+ T cell-induced colitis in Rag1−/− mice. This failure was likely due to reduced levels of critical Treg suppression genes, including Il2ra, Ctla4, Nt5e, and Gitr. Mechanistic studies using genome-wide binding analysis of Bcl11b show that Bcl11b directly regulates the expression of many of these genes by binding to genomic regulatory regions, both in mouse and human Treg cells, thus making Bcl11b ...
CD4+ Foxp3+ regulatory T (Treg) cells belong to a distinct T cell lineage which develops in the thymus and is essential for the prevention of self-reactivity by suppressing peripheral auto-reactive T cells that escape thymic negative selection. IL-2/IL-2R signaling is crucial and non-redundant for the development of thymic Treg cells, as well as the homeostasis and competitive fitness of peripheral Treg cells. The central role of IL-2 in Treg biology is exemplified by the uncontrolled massive lymphoproliferation associated with IL-2-/-, IL-2Rα-/- and IL-2Rβ-/- mice which typically die by 4-12 week of age. It is noteworthy that a restored normal percentage and number of peripheral Treg cells in Bim-/- IL-2-/- mice did not rescue these mice from severe autoimmunity. Instead, additional IL-2 was still required for the proper functioning of peripheral Bim-/- IL-2-/- Treg cells. Consistently, in the current studies, we found that the development of thymic Treg cells was blocked with mostly CD4+ CD25-
SJL mice exhibit a unique gender-dependent bias in their immune response. Males mount an anti-inflammatory Th2 response, whereas females react with an inflammatory Th1 response, which correlates with susceptibility to experimental autoimmune encephalomyelitis, a mouse model for multiple sclerosis. Castration as well as macrophage transfer from females reverses the male phenotype. Utilizing this mouse strain for the study of gender-dependent mechanisms of immune regulation, the role of CD25 regulatory T cells was examined. These cells maintain a Th2 environment in naïve males by regulating macrophage responsiveness. Transfer of macrophages from naïve CD25+-depleted males into untreated males results in a Th1 response after immunization demonstrating that regulatory T cells directly influence macrophage function. Males have a two-fold increase in the number of regulatory T cells compared to females, but no difference in cell surface marker expression or in vitro suppressive action was detected. ...
While modulation of regulatory T cell (Treg) function and adoptive Treg transfer are being explored as therapeutic modalities in the context of autoimmune diseases, transplantation and cancer, their role in HIV-1 pathogenesis remains less well defined. Controversy persists regarding their beneficial or detrimental effects in HIV-1 disease, which warrants further detailed exploration. Our objectives were to investigate if functional CD4(+) Tregs can be isolated and expanded from HIV-1-infected individuals for experimental or potential future therapeutic use and to determine phenotype and suppressive capacity of expanded Tregs from HIV-1 positive blood and tissue. Tregs and conventional T cell controls were isolated from blood and gut-associated lymphoid tissue of individuals with HIV-1 infection and healthy donors using flow-based cell-sorting. The phenotype of expanded Tregs was assessed by flow-cytometry and quantitative PCR. T-cell receptor ß-chain (TCR-β) repertoire diversity was investigated by
FOXP3+CD4+ regulatory T cells (Tregs) are critical for immune homeostasis and respond to local tissue cues, which control their stability and function. We explored here whether developmental endothelial locus-1 (DEL-1), which, like Tregs, increases during resolution of inflammation, promotes Treg responses. DEL-1 enhanced Treg numbers and function at barrier sites (oral and lung mucosa). The underlying mechanism was dissected using mice lacking DEL-1 or expressing a point mutant thereof, or mice with T cell-specific deletion of the transcription factor RUNX1, identified by RNA sequencing analysis of the DEL-1-induced Treg transcriptome. Specifically, through interaction with αvβ3 integrin, DEL-1 promoted induction of RUNX1-dependent FOXP3 expression and conferred stability of FOXP3 expression upon Treg restimulation in the absence of exogenous TGF-β1. Consistently, DEL-1 enhanced the demethylation of the Treg-specific demethylated region (TSDR) in the mouse Foxp3 gene and the suppressive ...
Naive CD4(+) cells differentiate into T helper (Th1, Th2, Th9, Th17) and regulatory T (Treg) cells to execute their immunologic function. Whereas TGF-β suppresses Th1 and Th2 cell differentiation, this cytokine promotes Th9, Th17 and Foxp3(+) regulatory T cells depending upon the presence of other cytokines. IL-6 promotes Th17, but suppresses regulatory T cell differentiation. Moreover, natural but not TGF-β-induced regulatory T cells convert into Th17 cells in the inflammatory milieu. Here an update of T cell differentiation and conversion, as well as underlying mechanisms are given.. ...
University of California, San Francisco, San Francisco, CA. Manipulating human regulatory T cells (Tregs) offers the opportunity to induce tolerance in a clinical setting. However, low numbers of antigen-specific Tregs and Treg instability upon prolonged expansion have hampered the implementation of Treg-based therapies. Chimeric antigen receptor (CAR) technology has greatly expedited the generation of tumor antigen- specific effector T (Teff) cells. CARs are synthetic receptors comprising an extracellular antigen-binding domain and an intracellular signaling domain. The latter is commonly a fusion of CD28 and CD3z, allowing for potent T cell activation directly downstream of antigen recognition. Adoption of the CAR platform for Treg engineering represents a promising strategy to generate custom-made antigen-specific Tregs for therapy. Yet, there are marked differences in function and signaling between Tregs and Teff cells. Here, we interrogated CAR-mediated signaling in human Tregs and Teff ...
To what extent proinflammatory Th17 cells and defects in Treg-mediated regulation contribute to the development of type 1 diabetes in humans is highly debated. Here we show that the PLNs of patients with type 1 diabetes, unlike their PB, have an altered immune status due to the expansion of Th17 cells and the presence of CD25bright T cells epigenetically imprinted to have a regulatory activity but which lack a proper function.. Increased Th17 cells in the PB of children with diabetes has been recently reported (8), and Tan and colleagues (9) have demonstrated that these circulating IL-17-producing T cells may reside mainly within the CD4+CD45RA−CD25intFOXP3low cells. Although expressing FOXP3, this latter cell subset does not have suppressive activity, but rather, it has a helper function and contains proinflammatory cytokine-producing cells (40,41). Our data demonstrate that the expansion of Th17 immunity is also present in the target organ of patients with long-term diabetes. However, this ...
Peripheral immune tolerance requires a finely controlled balance between tolerance to self-antigens and protective immunity against enteric and invading pathogens. Self-reactive T cells sometimes escape thymic clonal deletion, and can subsequently provoke autoimmune diseases such as type 1 diabetes (T1D) unless they are controlled by a network of tolerance mechanisms in the periphery, including CD4+ regulatory T cells (Treg) cells. CD4+ Treg cells are characterized by the constitutive expression of the IL-2Rα chain (CD25) and preferentially express the forkhead winged helix transcriptional regulator Foxp3. These cells have been shown to possess immunosuppressive properties towards various immune cell subsets and their defects are thought to contribute to many autoimmune disorders. Strong evidence shows that IL-2 is one of the important stimulatory signals for the development, function and fitness of Treg cells. The non-obese diabetic (NOD) mouse model, a prototypic model of spontaneous autoimmunity,
CD4(+)CD25+ regulatory T (Treg) cells are pivotal for the maintenance of self-tolerance, and their adoptive transfer gives protection from autoimmune diseases and pathogenic alloresponses after solid organ or bone marrow transplantation in murine model systems. In vitro, human CD4(+)CD25+ Treg cells display phenotypic and functional characteristics similar to those of murine CD4(+)CD25+ Treg cells: namely, hyporesponsiveness to T-cell receptor (TCR) stimulation and suppression of CD25- T cells. Thus far, the detailed characterization and potential clinical application of human CD4(+)CD25+ Treg cells have been hampered by their paucity in peripheral blood and the lack of appropriate expansion protocols. Here we describe the up to 40 000-fold expansion of highly purified human CD4(+)CD25high T cells in vitro through the use of artificial antigen-presenting cells for repeated stimulation via CD3 and CD28 in the presence of high-dose interleukin 2 (IL-2). Expanded CD4(+)CD25high T cells were ...
The upkeep of immune homeostasis requires regulatory T cells (Tregs). for a core property of regulatory T-cells. Regulatory T cells TPCA-1 (CD4 and CD8 Treg) dampen excessive immune responses and prevent or better autoimmune tissue damage while immune suppression exerted by Treg can impede anti-tumor immune responses. In contrast to effector T cells which rely on robust activation and differentiative plasticity Treg depend on preservation of a stable anergic and suppressive phenotype to maintain immune homeostasis (1 2 Although FoxP3+ CD4 Treg are remarkably stable (1 2 the genetic mechanisms that ensure phenotypic stability after expansion during inflammation infection Bombesin or autoimmunity i. e. conditions that most require maintenance of an inhibitory and anergic Treg phenotype are poorly comprehended. The Helios (Ikzf2) transcription factor (TF) is expressed by two regulatory T cell lineages- FoxP3+CD4+ and Ly49+CD8+ Treg (Fig. S1) TPCA-1 (3-6). To determine the contribution of Helios to ...
Inhibitory receptors on T cells, including lymphocyte activation gene 3 (LAG3), serve as brakes that limit immune-mediated damage to the host. LAG3 is expressed by exhausted conventional T cells in the tumor microenvironment and has emerged as a key target for tumor immunotherapy. The role of LAG3 in regulatory T cells (Tregs) has remained unclear. Using a mouse model of autoimmune diabetes, Zhang et al. report that Treg-specific deletion of LAG3 led to enhanced Treg proliferation and reduced the incidence of type 1 diabetes. Their studies highlight the cell-type dependence and context specificity of the role of LAG3 and call for a more holistic assessment of the functions of inhibitory receptors that emerge as targets for tumor immunotherapies. ...
FOXP3 is the master transcription factor of CD4+CD25+FOXP3+ T-regulatory (Treg) cells, and demethylation of the Treg-specific demethylation region (TSDR) of FOXP3 is considered a specific marker of stable, functionally competent thymic Tregs, allowing their discrimination from activated CD4+CD25+FOXP3+ T-effector cells. Assessment of TSDR demethylation in PBMC has thereby come to be regarded as a gold standard for calculating numbers of true Tregs. However, data regarding use of FOXP3 TSDR demethylation in PBMC were derived from healthy donor cells, i.e. mostly resting cells isolated from non-inflammatory conditions. Methods: We assessed FOXP3 TSDR demethylation in Tregs isolated from liver and kidney allograft recipients, as well as evaluating their number and phenotype (CD4, CD25, CD127, CTLA4, FOXP3), and assessed any correlations with the numbers of true Tregs calculated using FOXP3 TSDR demethylation in PBMC from the same samples. Results: Pediatric recipients had stable liver (n=53, 26 M) ...
The immunosuppressive effects of CD4⁺CD25⁺ regulatory T cells (Tregs) interfere with anti-tumor immune responses in cancer patients. In the first part of this work, we present a novel class of engineered Interleukin-2 (IL-2) analogues that antagonize the IL-2 receptor, for inhibiting Treg suppression. These antagonists are engineered for high affinity to the IL-2 receptor a subunit and low affinity to either the [beta] or [gamma] subunit, resulting in a signaling-deficient IL-2 analogue that sequesters the IL-2 receptor a subunit from wild type IL-2. Using this design, human and mouse IL-2 antagonists were generated with inhibition constants ranging from 200 pM to 5 nM in vitro. Genetic fusions with IgG2a Fc enhanced serum half-life up to 30 hours. In order to study the effects of IL-2 antagonism, Fc fragments with disrupted effector functions were used. Fc-antagonist fusions bound to but could not deplete peripheral Tregs. They downregulated CD25 on Tregs, but could not perturb Treg ...
Regulation of the immune response is important to avoid chronic inflammation and autoimmunity. Anergic/suppressive CD4+CD25+ T cells have been shown to be major contributors to this regulation. We have previously shown that the suppressive CD4+CD25+ T cells can suppress mitogenic and antigen-specific CD4+ T-cell responses in humans (EJI 2001, 31:1122; Immunology 2001, 104:6). In rheumatoid arthritis (RA), besides CD4+ T cells also monocytes play an important role in the disease process. Therefore we investigated whether the suppressive CD4+CD25+ T cells could affect monocyte activation as well as T-cell activation. CD4+ T cells and monocytes were isolated from peripheral blood mononuclear cells from healthy donors via MACS isolation techniques. CD4+ T cells were separated into CD4+CD25+ and CD4+CD25- T cells. T cells and monocytes were cocultured for two days without or with anti-CD3 mAb, after which proliferation, cytokine production and phenotypic markers were investigated. Coculture of ...
Definition of suppressor T cell in the Financial Dictionary - by Free online English dictionary and encyclopedia. What is suppressor T cell? Meaning of suppressor T cell as a finance term. What does suppressor T cell mean in finance?
It has been reported that a growing and heterogeneous group of regulatory cell modulate immune response. In particular, regulation of CD8+ T lymphocyte effector functions is critical for tissue homeostasis and immune tolerance control. Here, we report that the co-expression of CD3 and CD56 molecules identify a novel human regulatory T cell population exerting suppressive activity on proliferation, cytotoxicity and IFN- production of TCR-activated human CD8+ T lymphocytes. Regulatory functions of human circulating CD3+CD56+ T lymphocytes require cell-to-cell contact and are exerted in both autologous and allogeneic conditions. Of note, CD3+CD56+ T cells are reduced and functionally impaired in children affected by Type 1 Diabetes (T1D), at disease onset. Conversely the frequency of this cell subset is increased in patients with prostate cancer. Taken together, our findings reveal that freshly isolated human CD3+CD56+ cells specifically control activation of human CD8+ T lymphocytes. ...
Differential Effects of IL-12 on Tregs and Non-Treg T Cells: Roles of IFN-γ, IL-2 and IL-2R. . Biblioteca virtual para leer y descargar libros, documentos, trabajos y tesis universitarias en PDF. Material universiario, documentación y tareas realizadas por universitarios en nuestra biblioteca. Para descargar gratis y para leer online.
Regulatory T cells (Tregs) are potent suppressors of immune responses and are currently being clinically tested for their potential to stop or control undesired immune responses in autoimmunity, hematopoietic stem cell transplantation and solid organ transplantation. Current clinical approaches aim to boost Tregs in vivo either by using Treg-promoting small molecules/proteins and/or by adoptive transfer of expanded Tregs. However, the applicability of Treg-based immunotherapies continues to be hindered by technical limitations related to cell isolation and expansion of a pure, well-characterized and targeted Treg product. Efforts to overcome these limitations and improve Treg-directed therapies are now under intense investigation in animal models and pre-clinical studies. Here we review cell and protein engineering-based approaches that aim to target different aspects of Treg biology including modulation of IL-2 signaling or FOXP3 expression, and targeted antigen-specificity using transgenic T cell
The data presented in this study show that Ets-1 is required for normal development and function of T reg cells and that defects in this cell subset were responsible for some of the immunological disorders in Ets-1−/− mice. Viable young mutant animals had reduced numbers of T reg cells in the spleen, but the frequency in the thymus appeared normal. In both sites, Ets-1−/− T reg cells had an unusual phenotype in that they expressed CD103 (Fig. 4 B), a marker typical of cells that experienced antigen under certain inflammatory conditions (Huehn et al., 2004; Suffia et al., 2005). This raised the possibility that the majority of thymic Ets-1−/− T reg cells were antigen-experienced recirculating cells, thereby masking an important quantitative deficit in thymic development of these cells. This was indeed the case, as supported by the very low frequency of thymic T reg cells in FTOCs (Fig. 4 C), in 5-d-old newborns (not depicted), and in mixed WT/KO chimeras analyzed at relative early ...
Regulatory T cells (Tregs) act by suppressing the activation and effector functions of innate and adaptive immune responses. we show that equivalent conclusions were drawn from the mix of markers utilized to define Tregs no matter. Our outcomes also showed elevated appearance of cell routine markers (Ki67 and cyclin B) in Tregs from neglected infected individuals, that have been reduced by HAART. However, the Treg phenotype in untreated patients was not consistent with a higher level of generalized activation, as they expressed very low levels of CD69, slightly elevated levels of HLA-DR and comparable levels of GARP compared to Tregs from uninfected donors. Moreover, none of these markers was significantly changed by HAART. Treg expression of CTLA-4 and cytotoxic molecules was identical between patients and controls. The most striking difference in terms of functional molecules was the high expression of CD39 by Tregs in untreated patients, which HAART just handled partly. Launch Regulatory T ...
TGF-beta-induced myelin peptide-specific regulatory T cells mediate antigen-specific suppression of induction of experimental autoimmune encephalomyelitis.
Thymic derived naturally occurring CD25+ CD4+ T regulatory cells (Tregs) suppress immune responses, including transplantation. Here we discuss the capacity of dendritic cells (DCs) to expand antigen-specific Tregs, particularly polyclonal Tregs directed to alloantigens. Initial studies have shown th …
The mechanisms underlying the regulation of immune activation and immune exhaustion of T cells are unclear. Tregs have been investigated in HIV-1-infected subjects with conflicting results. Our data suggest that exhausted T cells are not only associated with hyperactivated T cells but also with reduced numbers of Tregs. When we determined the CD4+CD25bright FoxP3+ Treg population in proportion to CD4+CD25bright FoxP3 negative non-Treg activated CD4 T cells, we noted that the proportions were altered in favor of the non-Treg-activated CD4 T cells in HIV-positive subjects. In this analysis, however, the changes observed in Treg frequency could have simply been a consequence of changes in activated CD4+ T-cell frequency. On the other hand, the percentage of Tregs in the total CD4+ T-cell population of the viremic patients was also significantly lower as compared with aviremic patients and to healthy controls. As activated CD8 T cells were also clearly higher in viremic patients, this provides ...
Regulatory T cells help maintain intestinal homeostasis by preventing inappropriate innate and adaptive immune responses. CD4(+) T cells that express Foxp3 and Tr1-like cells that produce IL-10 comprise the major regulatory populations in the intestine. CD4(+)Foxp3(+) T cells play an important functional role in promoting tolerance of the flora and dietary proteins. Tr1-like cells can be generated in conditions that also promote effector T cell responses and may serve a similar function. In this review, we discuss the signals specific to the gastrointestinal tract that support both regulatory cell types and their distinct modes of action in the mesenteric lymph nodes and intestinal tissues. Dysregulation of intestinal immune homeostasis occurs in inflammatory bowel disease and can also be observed in graft-versus-host disease, tumor immunotherapy regimens, and acute HIV infection.
In the United States, asthma prevalence is particularly high among urban children. Although the underlying immune mechanism contributing to asthma has not been identified, having impaired T regulatory (Treg) cells at birth may be a determining factor in urban children. The objective of this study was to compare Treg phenotype and function in cord blood (CB) of newborns to those in peripheral blood (PB) of a subset of participating mothers. Treg numbers, expression, and suppressive function were quantified in subjects recruited prenatally from neighborhoods where ≥ 20% of families have incomes below the poverty line. Proportion of Treg cells and expression of naïve (CD45RA) or activated (CD45RO, CD69, and HLA-DR) markers in CD4+T cells was measured by flow cytometry. Treg suppressive capacity was determined by quantifying PHA-stimulated lymphocyte proliferation in mononuclear cell samples with and without CD25 depletion. In an urban cohort of 119 newborns and 82 mothers, we found that newborns had
TY - JOUR. T1 - Increased CD4+ CD25+ T regulatory cell activity in trauma patients depresses protective Th1 immunity. AU - MacConmara, Malcolm P.. AU - Maung, Adrian A.. AU - Fujimi, Satoshi. AU - McKenna, Ann M.. AU - Delisle, Adam. AU - Lapchak, Peter H.. AU - Rogers, Selwyn. AU - Lederer, James A.. AU - Mannick, John A.. PY - 2006/10/1. Y1 - 2006/10/1. N2 - OBJECTIVES: We recently reported increased CD4 CD25 T regulatory (Treg) activity after burn injury in mice. This study sought to determine if Tregs mediate the reduction in TH1-type immunity after serious injury in man and if Treg function is altered by injury. METHODS: Peripheral blood was withdrawn from 19 consenting adult patients (35.1 ± 16.3 years of age) with Injury Severity Scores (ISS) 36.6 ± 13.9 on days 1 and 7 after trauma and from 5 healthy individuals. CD4 T cells were purified and sorted into Treg (CD25) and Treg-depleted populations. After activation of cells with anti-CD3/CD28 antibody, production of the TH1-type cytokine ...
Recognition of self-antigens is required for regulatory T (Treg) cells to exert dominant tolerance. However, the mechanism by which self-reactive thymocytes are diverted into the Treg cell subset is unclear. To address this question, we looked for the immediate precursors to Treg cells within Foxp3( …
FOXP3+ regulatory T (Treg) cells have crucial roles in maintaining self-tolerance and modulating adaptive immune responses. Functional studies of Treg cells have been hampered by a lack of suitable cell-surface markers that specifically enable their purification without contamination by non-regulatory CD25+ effector T cells. Two recent studies have demonstrated that downregulation of the interleukin-7 receptor (CD127) distinguishes Treg cells from activated T cells, facilitating both Treg-cell purification and their functional characterization in human diseases. CD127 uniquely enables the purification of FOXP3+ Treg cells and, potentially, also adaptive regulatory T-cell subsets from the CD4+CD25- T-cell population.
Scurfy mice are deficient in regulatory T cells (Tregs), develop a severe, generalized autoimmune disorder that can affect almost every organ and die at an early age. Some of these manifestations resemble those found in systemic lupus erythematosus (SLE). In addition, active SLE is associated with low Treg numbers and reduced Treg function, but direct evidence for a central role of Treg malfunction in the pathophysiology of lupus-like manifestations is still missing. In the present study, we characterize the multiorgan pathology, autoantibody profile and blood count abnormalities in scurfy mice and show their close resemblances to lupus-like disease. Scurfy mice have dysfunctional Tregs due to a genetic defect in the transcription factor Forkhead box protein 3 (Foxp3). We analyzed skin, joints, lung and kidneys of scurfy mice and wild-type (WT) controls by conventional histology and immunofluorescence (IF) performed hematological workups and tested for autoantibodies by IF, immunoblotting and enzyme
T cell receptor (TCR)-dependent regulatory T cell (Treg) activity controls effector T cell (Teff) function and is inhibited by the inflammatory cytokine tumor necrosis factor-α (TNF-α). Protein kinase C-θ (PKC-θ) recruitment to the immunological synapse is required for full Teff activation. In contrast, PKC-θ was sequestered away from the Treg immunological synapse. Furthermore, PKC-θ blockade enhanced Treg function, demonstrating PKC-θ inhibits Treg-mediated suppression. Inhibition of PKC-θ protected Treg from inactivation by TNF-α, restored activity of defective Treg from rheumatoid arthritis patients, and enhanced protection of mice from inflammatory colitis. Treg freed of PKC-θ-mediated inhibition can function in the presence of inflammatory cytokines and thus have therapeutic potential in control of inflammatory diseases.. ...
TY - JOUR. T1 - Kidney GATA3+ regulatory T cells play roles in the convalescence stage after antibody-mediated renal injury. AU - Sakai, Ryota. AU - Ito, Minako. AU - Komai, Kyoko. AU - Iizuka-Koga, Mana. AU - Matsuo, Kazuhiko. AU - Nakayama, Takashi. AU - Yoshie, Osamu. AU - Amano, Koichi. AU - Nishimasu, Hiroshi. AU - Nureki, Osamu. AU - Kubo, Masato. AU - Yoshimura, Akihiko. N1 - Funding Information: We would like to thank Mari Ikeda, Yoshiko Noguchi, Yasuko Hirata, and Yukiko Tokifuji (Keio University) for their technical assistance; Mika Inoue (Keio University) and Kasane Imura-Kishi (The University of Tokyo) for their help in manuscript preparation; and Yuzo Koda (Keio University) for his invaluable insights. R.S. is supported by a Tadamitsu Kishimoto Kibou Projects Scholarship for Doctoral Students in Immunology. This work was supported by JSPS KAKENHI (S) JP17H06175, Challenging Research (P) JP18H05376, and AMED-CREST JP 20gm1110009 grants to A.Y.; JSPS KAKENHI 17K15667, 19H04817, and ...
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Recent results have shown a correlation between survival and frequency of tumour infiltrating T lymphocytes in colorectal cancer patients. However, it remains unclear whether the frequency of regulatory T cells is higher in colorectal cancer as compared to normal colon. To address this question we analysed the frequency and function of regulatory T cells in the peripheral blood and tumour infiltrating lymphocytes of colorectal cancer patients. The proportion of regulatory T cells in the peripheral blood of colorectal cancer patients (mean 8%) was significantly higher than that in normal controls (mean 2.2%). There were significantly more regulatory T cells in tumour infiltrating lymphocytes (mean 19.2%) compared to lymphocytes from an autologous non-malignant portion of the colon (mean 9%). Regulatory T cells from colorectal cancer patients were FOXP3 positive and suppressed the proliferation of autologous CD4+ CD25- cells. A higher density of tumour infiltrating regulatory T cells was found in patients
TY - JOUR. T1 - Engineered T regulatory type 1 cells for clinical application. AU - Gregori, S. AU - Roncarolo, MG. PY - 2018. Y1 - 2018. N2 - T regulatory cells, a specialized subset of T cells, are key players in modulating antigen (Ag)-specific immune responses in vivo. Inducible T regulatory type 1 (Tr1) cells are characterized by the co-expression of CD49b and lymphocyte-activation gene 3 (LAG-3) and the ability to secrete IL-10, TGF-β, and granzyme (Gz) B, in the absence of IL-4 and IL-17. The chief mechanisms by which Tr1 cells control immune responses are secretion of IL-10 and TGF-β and killing of myeloid cells via GzB. Tr1 cells, first described in peripheral blood of patients who developed tolerance after HLA-mismatched fetal liver hematopoietic stem cell transplantation, have been proven to modulate inflammatory and effector T cell responses in several immune-mediated diseases. The possibility to generate and expand Tr1 cells in vitro in an Ag-specific manner has led to their ...
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CD4+ T cells play key roles in the regulation of immune responses against pathogenic infectious antigens via development into effector T helper and induced regulatory T (iTreg) cells. Particularly, CD4+CD25+Foxp3+ iTreg cells are crucial for maintaining immune homeostasis and controlling inflammatory diseases. Anti-inflammatory drugs that enhance iTreg cell generation would be effective at preventing and treating inflammatory and autoimmune diseases. In this study, we examined whether anti-malarial and anti-arthritic amodiaquine (AQ) could affect iTreg cell development. Despite the anti-proliferative activity of AQ, AQ only moderately decreased iTreg cell proliferation but substantially increased IL-2 production by iTreg cells. Furthermore, AQ dose-dependently increased iTreg cell development and significantly upregulated iTreg cell markers including CD25. Interestingly, CD25 expression was decreased at later stages of iTreg cell development but was sustained in the presence of AQ, which was ...
Immune-suppressive cellular immunotherapy requires large numbers of antigen-specific regulatory T cells (Treg cells), lymphocytes that suppress certain immune responses. Together, three papers in this issue of Science Translational Medicine describe protocols for the ex vivo expansion of human Treg cells and assess the immune-suppressive function of ex vivo-manipulated Treg cells after transfer into humanized mouse disease models. Along with recent phase I clinical trial results, these new data provide a platform for clinical use of Treg cells as personalized therapeutic agents for the treatment of autoimmune diseases, graft-versus-host disease, and transplant rejection.. ...
This simple picture has been complicated by the discovery of two further contrasting lineages of cells. The IL-17-secreting and IL-22-secreting pro-inflammatory Th17 cell has been implicated in combating extracellular bacterial and fungal infections and has been linked to a number of mouse models of autoimmune disease.5 In contrast, the anti-inflammatory induced T regulatory (iTreg) cell, characterized by the expression of the transcription factor forkhead box P3, inhibits proliferation and cytokine production by other T cells.5 Despite their opposite roles, in mice, Th17 and iTreg cells are both induced by activation in the presence of the cytokine transforming growth factor beta (TGF-beta). The combination of TGF-beta with the STAT3-activating cytokine IL-6 produces a Th17 cell,6 whereas the combination of TGF-beta and the STAT5-activating cytokine IL-2 induces iTreg cell differentiation.7 The key regulating cytokines in humans are not fully understood, although many recent articles have ...
Genetic perturbations of the transcription factor Forkhead Box P1 (FOXP1) are causative for severe forms of autism spectrum disorder that are often comorbid with intellectual disability. Recent work has begun to reveal an important role for FoxP1 in brain development, but the brain-region-specific contributions of Foxp1 to autism and intellectual disability phenotypes have yet to be determined fully. Here, we describe Foxp1 conditional knock-out (Foxp1cKO) male and female mice with loss of Foxp1 in the pyramidal neurons of the neocortex and the CA1/CA2 subfields of the hippocampus. Foxp1cKO mice exhibit behavioral phenotypes that are of potential relevance to autism spectrum disorder, including hyperactivity, increased anxiety, communication impairments, and decreased sociability. In addition, Foxp1cKO mice have gross deficits in learning and memory tasks of relevance to intellectual disability. Using a genome-wide approach, we identified differentially expressed genes in the hippocampus of Foxp1cKO
Results Skewing was not associated with increased age in patients with SSc, in contrast to the control population (r=0.45, p,0.0001). Taking this into account, a significantly higher frequency of skewed XCI was found in patients with SSc compared with controls (p=0.001). No difference in skewing was observed between the immune cell subsets. In addition, a higher concentration of Foxp3+ cells exhibiting a lower Foxp3 mean fluorescence intensity was found in the patients with SSc, with profound XCI skewing (both p,0.001) associated with less efficient suppressive activity (p=0.012). ...
positive regulation of CD4-positive, CD25-positive, alpha-beta regulatory T cell differentiation - Ontology Report - Chinchilla Research Resource Database
The evolution of immune blockades in tumors limits successful anti-tumor immunity, but the mechanisms underlying this process are not fully understood. Depletion of regulatory T cells (Tregs), a T cell subset that dampens excessive inflammatory and autoreactive responses, can allow activation of tumor-specific T cells. However, cancer immunotherapy studies have demonstrated that a persistent failure of activated lymphocytes to infiltrate tumors remains a fundamental problem. In evaluating this issue, we found that despite an increase in T cell activation and proliferation following Treg depletion there was no significant association with tumor growth rate. In contrast, there was a highly significant association between low tumor growth rate and the extent of T cell infiltration. Further analyses revealed a total concordance between low tumor growth rate, high T cell infiltration and the presence of high endothelial venules (HEV). HEV are blood vessels normally found in secondary lymphoid tissue ...
Treg-cell function is compromised in rheumatoid arthritis (RA). As the master regulator of Treg cells, FOXP3 controls development and suppressive function. Stable Treg-cell FOXP3 expression is epigenetically regulated; constitutive expression requires a demethylated Treg-specific demethylated region. Here, we hypothesised that methylation of the FOXP3 locus is altered in Treg cells of established RA patients. Methylation analysis of key regulatory regions in the FOXP3 locus was performed on Treg cells from RA patients and healthy controls. The FOXP3 Treg-specific demethylated region and proximal promoter displayed comparable methylation profiles in RA and healthy-donor Treg cells. We identified a novel differentially methylated region (DMR) upstream of the FOXP3 promoter, with enhancer activity sensitive to methylation-induced silencing. In RA Treg cells we observed significantly reduced DMR methylation and lower DNA methyltransferase (DNMT1/3A) expression compared with healthy Treg cells. Furthermore,
Experimental evidence supporting the possibility of antigen-specific Treg in atherosclerosis does exist. Atherosclerotic disease in ApoE−/− can be attenuated by adoptive transfer of HSP60-specific Treg generated in vitro by stimulation of naïve T cells with HSP60 and immature dendritic cells.13 Furthermore, induced mucosal tolerance to HSP60 reduces atherosclerosis in mice.14,15 In this issue of Arteriosclerosis, Thrombosis, and Vascular Biology, Van Puijvelde et al also present data demonstrating that induction of oral tolerance to HSP60 and to small HSP60-peptide significantly reduces atherosclerotic plaque size in Ldlr−/− mice.16 This study goes beyond the previous studies with similar findings by showing the tolerogenic and atheroprotective effect is related to increased Treg activity. Oral tolerance toward HSP60 in the atherosclerotic mice was associated with increased Treg numbers in lymphoid tissues, and with increased ex vivo production of IL-10 and TGF-β by T cells from the ...
Hepatocellular carcinoma (HCC) is a common malignant tumour, especially in Asia. Its prognosis is poor, and there are limited methods for predicting patient survival. This study was carried out to analyse the prognostic value of tumour-infiltrating lymphocytes (TILs), especially regulatory T cells (Tregs), in HCC patients. TILs were analysed in 57 randomly selected HCC patients. The prognostic effects of groups with high and low numbers were evaluated by the Kaplan-Meier and Cox model analyses. Although higher densities of CD3(+), CD4(+), and CD8(+) cytotoxic lymphocytes (CTLs) as well as CD56(+) NK cells and CD68(+) macrophages were observed in peritumoural tissue, increased numbers of forkhead/winged helix transcription factor P3(+) (FOXP3(+)) Tregs were found in intratumoural tissue. Additionally, regarding ICOS(+) FOXP3(+) Tregs, an increased prevalence in carcinoma was not only associated with the absolute number but also with the percentage of FOXP3(+) cells. Higher Treg levels in tumour ...
A key role of Foxp3 in the development of natural T reg cells has been suggested from the molecular characterization of the scurfy mouse mutant. These mice, which suffer from a fatal lymphoproliferative disorder, harbor a mutated foxp3 gene coding for a product that lacks the forkhead domain (13). Scurfy mice receiving CD25+CD4+ T reg cells from WT mice remained virtually disease free (11). Furthermore, transduction of mutant Foxp3, lacking the forkhead domain, failed to confer suppressive activity to naive CD4+ T cells, in contrast to full-length Foxp3 (12). Thus, it is widely accepted that an intrinsic T cell failure to generate functional CD4+ T reg cells is the main cause of the fatal autoimmune disease in scurfy mice, although an additional role of the scurfy mutation in nonhematopoietic cells has been suggested (14, 15). Moreover, it remains unknown whether the mere absence of functional Foxp3+ T reg cells is sufficient to provoke the development of the scurfy phenotype or whether those ...
IL-15 drives chronic inflammation in several human diseases. We have recently shown that IL-15 inhibits the immunosuppressive effects of TGF-beta through blockage of the Smad3-signaling pathway. Data pointing to reciprocal interactions between TGF-beta and CD4(+) regulatory T cells led us to investigate the impact of IL-15 on the de novo generation and function of regulatory T cells in humans. Our data indicate that IL-15 does not counteract, but rather promotes the effect of TGF-beta on the de novo generation of regulatory T cells (Treg). Thus, in the presence of TGF-beta, IL-15 enhanced the acquisition of regulatory functions by CD4(+)CD25(-) T cells stimulated by anti-CD3 and anti-CD28 Abs. In contrast, IL-15 impaired the functions of Tregs by acting on effector CD4 and CD8 T cells. Accordingly, in the presence of IL-15, proliferation and IFN-gamma production by peripheral CD4 and CD8 T cells could not be efficiently inhibited by Tregs. IL-15-induced resistance of effector T cells to Tregs resulted
T regulatory lymphocytes were shown to be partly responsible for immune tolerance to cancer cells. In that respect these cells oppose to the mounting of
Costimulatory signals by CD28 are critical for thymic regulatory T-cell (Treg) development. To determine the functional relevance of CD28 for peripheral Treg post thymic selection, we crossed the widely used Forkhead box protein 3 (Foxp3)-CreYFP mice to mice bearing a conditional Cd28 allele. Treg-specific CD28 deficiency provoked a severe autoimmune syndrome as a result of a strong disadvantage in competitive fitness and proliferation of CD28-deficient Tregs. By contrast, Treg survival and lineage integrity were not affected by the lack of CD28. This data demonstrate that, even after the initial induction requirement, Treg maintain a higher dependency on CD28 signalling than conventional T cells for homeostasis. In addition, we found the Foxp3-CreYFP allele to be a hypomorph, with reduced Foxp3 protein levels. Furthermore, we report here the stochastic activity of the Foxp3-CreYFP allele in non-Tregs, sufficient to recombine some conditional alleles (including Cd28) but not others (including ...
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Regulatory T cells (Tregs) can be anti-tumorigenic or pro-tumorigenic in colorectal cancer (CRC) depending on the presence of different Treg subsets with various immunosuppressive molecules. Some studies reported the phenotypic characteristics of tumor-infiltrating immune cells in CRC but limited studies have focused on the co-expression of suppressive molecules on immune cells. The aim of this study was to characterize immune cells in the tumor microenvironment (TME), compared to paired adjacent non-tumor colon tissue of CRC patients. Additionally, we investigated co-expression of immunosuppressive molecules on different Treg subsets in the TME, normal colon tissue and peripheral blood of CRC patients and healthy donors. In this preliminary study, we report that the majority of CD3+ T cells in the TME are CD4+ cells with high co-expression of PD-1/CTLA-4 and PD-1/CD39 molecules. Levels of CD4+FoxP3+Helios+ Tregs were significantly increased in the TME. Furthermore, we observed increased levels of PD-1
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0092]It was reasoned that if iDC could promote Treg cell survival, enriching the CD4+ population into CD25+ or CD25- prior to iDC priming would allow for tracking the development of Treg cells. Also, if repetitive stimulation of naive CD4+ cells by allogeneic iDC was inducing development of a regulatory-like T cell population that upregulated CD25 expression, increased CD25 expression in the CD4+CD25- enriched population over a short term coculture could be observed. CD4+CD25+ and CD4+CD25- cells were enriched from CD4+ T cells by MACS. Either CD4+CD25+ or CD4+CD25- cells with allogeneic iDCs, derived from 7 day culture of CD14+PBMCs with IL-4 and GM-CSF, were cocultured. Initially, MACS enriched a population of CD4+CD25+ cells appearing to have a uniform level of CD25 expression, as determined by flow cytometry (FIG. 1). However, over a three day time course, two major populations emerged from the original CD25+ population (FIG. 1). One population retained CD25 expression (referred to as ...
FOXP3+ regulatory T cells (Treg) control T cell activation and effector functions and are key players in immune homeostasis and self-tolerance. Given their central role in preventing autoimmune responses, Treg are considered important targets for the treatment of autoimmune inflammation and several strategies are being explored to enhance Treg numbers ... read more or function for the treatment of autoimmune disease. In addition, numerous research groups have studied the presence, phenotype and function of Treg in patients with autoimmune disease. Whether deficiencies in Treg underlie human autoimmune pathology, however, is still a subject of debate. In this thesis we investigated Treg numbers and function in patients with juvenile idiopathic arthritis (JIA), one of the most common autoimmune diseases in children, characterized by chronic inflammation of the joints. In these patients Treg from the site of inflammation can be studied, because during treatment synovial fluid is taken from inflamed ...
TY - JOUR. T1 - The progress and prospect of regulatory T cells in autoimmune diseases. AU - Zhang, Ximei. AU - Olsen, Nancy. AU - Zheng, Song Guo. PY - 2020/1/1. Y1 - 2020/1/1. N2 - Regulatory T cells (Treg) are an important immune cell population, playing a crucial role in regulating immune tolerance and preventing autoimmune diseases. These cells consist of various cell sub-populations and generally have an immunoregulatory or suppressive role against immune responses. They also have a different cell heterogeneity and each populations has own biological characteristics. Treg deficiency, reduction, instability, reduced vitality and dysfunction all account for multiple autoimmune diseases. In this review, we have systemically reviewed Treg classification, phenotypic features, regulation of Foxp3 expression, plasticity and stability of Treg as well as their relationship with several important autoimmune diseases. We particularly focus on why and how inflammatory and diet environments affect the ...
Diacylglycerol (DAG) is a critical second messenger that mediates T cell receptor (TCR)-stimulated signaling. The abundance of DAG is reduced by the diacylglycerol kinases (DGKs), which catalyze the conversion of DAG to phosphatidic acid (PA) and thus inhibit DAG-mediated signaling. In T cells, the predominant DGK isoforms are DGKα and DGKζ, and deletion of the genes encoding either isoform enhances DAG-mediated signaling. We found that DGKζ, but not DGKα, suppressed the development of natural regulatory T (Treg) cells and predominantly mediated Ras and Akt signaling downstream of the TCR. The differential functions of DGKα and DGKζ were not attributable to differences in protein abundance in T cells or in their localization to the contact sites between T cells and antigen-presenting cells. RasGRP1, a key DAG-mediated activator of Ras signaling, associated to a greater extent with DGKζ than with DGKα; however, in silico modeling of TCR-stimulated Ras activation suggested that a ...
Mediators of Inflammation is a peer-reviewed, Open Access journal that publishes original research and review articles on all types of inflammatory mediators, including cytokines, histamine, bradykinin, prostaglandins, leukotrienes, PAF, biological response modifiers and the family of cell adhesion-promoting molecules.
© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. CD4+CD25+Foxp3+ regulatory T (Treg) cells mediate immunological self-tolerance and suppress immune responses. Retinoic acid (RA), a natural metabolite of vitamin A, has been reported to enhance the differentiation of Treg cells in the presence of TGF-β. In this study, we show that the co-culture of naive T cells from C57BL/6 mice with allogeneic antigen-presenting cells (APCs) from BALB/c mice in the presence of TGF-β, RA, and IL-2 resulted in a striking enrichment of Foxp3+ T cells. These RA in vitro-induced regulatory T (RA-iTreg) cells did not secrete Th1-, Th2-, or Th17-related cytokines, showed a nonbiased homing potential, and expressed several cell surface molecules related to Treg-cell suppressive potential. Accordingly, these RA-iTreg cells suppressed T-cell proliferation and inhibited cytokine production by T cells in in vitro assays. Moreover, following adoptive transfer, RA-iTreg cells maintained Foxp3 expression and their suppressive
In this report, we describe the unexpected finding that cetuximab-based therapy is associated with an increase in CTLA-4+Foxp3+ Treg in the circulation and in the microenvironment in treated patients with HNSCC from two independent clinical trial cohorts. Indeed, higher levels of Treg correlated with worse prognosis in cetuximab-treated patients with HNSCC, as recently seen in lung cancer after neoadjuvant chemotherapy (31). For the first time, we also show that intratumoral NK cell activation and cytotoxicity occurs during cetuximab therapy, which is primarily inhibited by Treg-derived TGFβ1, providing a mechanism for their suppressive effect and impact on clinical course of the disease. Furthermore, we demonstrated that NK cells can selectively eliminate intratumoral Treg in the presence of ipilimumab, which induces recovery of cetuximab ADCC activity from Treg suppression. Importantly, the suppressive effect of these Treg could be substantially abrogated by ipilimumab-mediated NK cell ...
Lieske, Nora Valeska; Tonby, Kristian; Kvale, Dag; Dyrhol-Riise, Anne Ma & Tasken, Kjetil (2015). Targeting tuberculosis and HIV infection-specific regulatory T cells with MEK/ERK signaling pathway inhibitors. PLOS ONE. ISSN 1932-6203. 10:e0141903(11) . doi: 10.1371/journal.pone.0141903 Fulltekst i vitenarkiv. Vis sammendrag Human regulatory T cells (Tregs) are essential in maintaining immunological tolerance and suppress effector T cells. Tregs are commonly up-regulated in chronic infectious diseases such as tuberculosis (TB) and human immunodeficiency virus (HIV) infection and thereby hamper disease-specific immune responses and eradication of pathogens. The MEK/ERK signaling pathway is involved in regulation of the FoxP3 transcription factor, which directs a lineage-specific transcriptional program to define Tregs and control their suppressive function. Here, we aimed to target activation of disease-specific Tregs by inhibition of the MEK/ ERK signaling pathway based on the hypothesis that ...
TY - JOUR. T1 - Regulatory T Cell Transmigration and Intravascular Migration Undergo Mechanistically Distinct Regulation at Different Phases of the Inflammatory Response. AU - Snelgrove, Sarah L.. AU - Abeynaike, Latasha D.. AU - Thevalingam, Sukarnan. AU - Deane, James A.. AU - Hickey, Michael J.. PY - 2019/12/1. Y1 - 2019/12/1. N2 - Regulatory T cells (Tregs) play important roles in limiting inflammatory responses in the periphery. During these responses, Treg abundance in affected organs increases and interfering with their recruitment results in exacerbation of inflammation. However, the mechanisms whereby Tregs enter the skin remain poorly understood. The aim of this study was to use intravital microscopy to investigate adhesion and transmigration of Tregs in the dermal microvasculature in a two-challenge model of contact sensitivity. Using intravital confocal microscopy of Foxp3-GFP mice, we visualized endogenous Tregs and assessed their interactions in the dermal microvasculature. Four ...
Results Th17 cells were decreased in the peripheral blood of RA patients, while OA patients had surprisingly an altered ratio of CD25+Tregs and Tr1 cells in circulation. In synovial tissues Th17 cells, TFH and regulatory T cell subsets were enriched among CD4+ T cells in RA as compared to OA patients, while frequencies of Th1 cells were similar. RA patients had higher serum levels of IL-17, IL-10 and BAFF, while serum IL-21 was elevated in both RA and OA patients. Importantly, serum levels of IL-17, IL-10 and BAFF were enhanced only in patients with active RA or with detectable autoantibodies. Moreover, BAFF and IL-17 levels in synovial fluid were also higher in RA as compared to OA patients, while IL-10 concentrations were similar. B cells from synovial fluid spontaneously released high amounts of IgG in the absence of CD4+ helper T cells, and regulatory T cell subsets were unable to suppress B cell IgG production.. ...
BACKGROUND: Compared with rare CD4+CD25+ regulatory T cells (Tregs), CD4+CD25- T cells are abundant in peripheral blood. Studies have demonstrated that tumors can convert naive CD4+CD25- T cells into CD4+CD25+Foxp3+ Tregs; however, the potential application of the converted Tregs in transplant medicine has not well demonstrated.. MATERIALS AND METHODS: CD4+CD25- T cells isolated cultured for 5 d in various combinations of cell culture medium and conditioned medium from RenCa cells. Foxp3 levels were determined by flow cytometry and real-time polymerase chain reaction. BALB/c mouse mononuclear cells (responder) combined with different ratios of the converted CD4+CD25+ Tregs were co-cultured with inactivated C57BL/6 mononuclear cells (stimulator) in one-way mixed lymphocyte reaction (MLR). In addition, the converted Tregs were transferred into a mouse skin transplant model, and graft histology, survival time, and delayed-type hypersensitivity were assessed.. RESULTS: CD4+CD25- T cells cultured in ...
The CD25+CD49d- Regulatory T Cell Isolation Kit was developed for the isolation of CD4+CD25+CD49d- regulatory T cells from human PBMCs in a two-step procedure. - Italia
The CD25+CD49d- Regulatory T Cell Isolation Kit was developed for the isolation of CD4+CD25+CD49d- regulatory T cells from human PBMCs in a two-step procedure. | USA
Ley K, Smith E, Stark MA (2006). "IL-17A-producing neutrophil-regulatory Tn lymphocytes". Immunologic Research. 34 (3): 229-42 ... May 2006). "Selective regulatory function of Socs3 in the formation of IL-17-secreting T cells". Proceedings of the National ... Increased concentration of IL-6 alters the epidermal environment by decreasing the ability of T regulatory cells to control the ... "First in the world regulatory approval of Novartis' Cosentyx(TM) in Japan for both psoriasis and psoriatic arthritis". Novartis ...
... is a regulatory protein on B lymphocytes. The cytoplasmic tail of CD72 contains two potential immunoreceptor tyrosine- ... These features suggest a negative regulatory role for CD72. CD72 is a nonredundant regulator of B-cell development and a ...
TNFRSF25 is also highly expressed by FoxP3 positive regulatory T lymphocytes. TNFRSF25 is activated by a monogamous ligand, ... This receptor is expressed preferentially by activated and antigen-experienced T lymphocytes. ... stimulates profound and highly specific proliferation of FoxP3+ regulatory T cells from their 8-10% of all CD4+ T cells to 35- ... the majority of T cells that regularly encounter cognate antigen are FoxP3+ regulatory T cells. Stimulation of TNFRSF25, in the ...
regulatory T-lymphocytes have a limited capability to control these cells. In the late stage, the extent of inflammation ... They are also involved in intensification of the function of regulatory T-lymphocytes and in the induction of apoptosis of ... leukocytes and lymphocytes), and red blood cells. Although some of these microvesicle populations occur in the blood of healthy ... cytotoxic T-lymphocytes, because microvesicles released from a tumor cell contain Fas ligand and TRAIL. They prevent ...
... and regulatory T lymphocytes. Thus, CCL1 mainly acts as a chemoattractant for monocytes/macrophages, T lymphocytes, specially ... CCL1 is secreted by activated monocytes/macrophages, T lymphocytes and endothelial cells. CCL1 binds to the chemokine receptor ... most likely leading to an influx of lymphocytes and monocytes and thus to an adaptive immune response. Because CCL1 binds to ... Th2-differentiated T cells and a subset of T regulatory cells in vitro into inflammatory siter. It can also attract NK cells, ...
González-Amaro R, Marazuela M (April 2016). "T regulatory (Treg) and T helper 17 (Th17) lymphocytes in thyroid autoimmunity". ... This in turn results in temporary lymphocyte retention in the lymph organs. It is thought that retention of lymphocytes in the ... is involved in lymphocyte proliferation and functions as a signal-transmitting receptor in lymphocytes, including natural ... Most lymphocytes express sphingosine-1-phosphate receptors (S1P1-5), which are G protein-coupled receptors located in the cell ...
Interleukin 10 is produced by regulatory T lymphocytes, B cells, and monocytes. It is a homodimer that functions through the IL ... is involved in immuno-regulatory responses IL-24 produced by activated monocytes and T-cells. IL-26 is a newly discovered ...
E proteins are involved in the development of lymphocytes. They initiate transcription by binding to regulatory E-box sequences ... E proteins play a critical role in lymphopoiesis, and the encoded protein is required for B and T lymphocyte development. This ... E proteins activate transcription by binding to regulatory E-box sequences on target genes as heterodimers or homodimers, and ... Quong MW, Romanow WJ, Murre C (2002). "E protein function in lymphocyte development". Annual Review of Immunology. 20: 301-22. ...
These results strongly support the regulatory role of TIRC7 signalling pathway in lymphocytes. TCIRG1 mutations affect the a3 ... Upon lymphocyte activation TIRC7 is upregulated to engage HLA-DRα2 and induce apoptotic signals in human CD4+ and CD8+ T-cells ... The negative immune regulatory role of TIRC7 is furthermore supported by the fact that TIRC7 knock out mice exhibits an ... The induction of TIRC7 in IL-10 secreting T regulatory cells and the prevention of colitis in the presence of TIRC7 positive T ...
"Entrez Gene: SIPA1 signal-induced proliferation-associated gene 1". Minato N (1997). "[Regulatory mechanisms of lymphocyte ... It exhibits a specific GAP activity for Ras-related regulatory proteins Rap1 and Rap2, but not for Ran or other small GTPases. ...
It is located on chromosome 1p13 and expressed in lymphocytes. It acts as a negative regulator of T-cell activation. Mutation ... This gene is the second major immune-regulatory gene related to autoimmune thyroid disease. CTLA-4 gene polymorphisms may ... It is also characterized by invasion of the thyroid tissue by leukocytes, mainly T-lymphocytes. A rare but serious complication ... Activation of cytotoxic T-lymphocytes (CD8+ T-cells) in response to cell-mediated immune response affected by helper T- ...
Fanzo JC, Hu CM, Jang SY, Pernis AB (2003). "Regulation of lymphocyte apoptosis by interferon regulatory factor 4 (IRF-4)". J. ... "Cloning of human lymphocyte-specific interferon regulatory factor (hLSIRF/hIRF4) and mapping of the gene to 6p23-p25". Genomics ... "Interferon regulatory factor 4 is involved in Epstein-Barr virus-mediated transformation of human B lymphocytes". J Virol. 82 ( ... Interferon regulatory factor 4 also known as MUM1 is a protein that in humans is encoded by the IRF4 gene, located at 6p25-p23 ...
Later was shown that the effect of monoclonal antibodies is formation of regulatory T lymphocytes. It has been shown that ... was originally used by Gershon and Kondo in 1970 for suppression of naive lymphocyte populations by cells with regulatory ... During a tolerant state potential effector cells remain but are tightly regulated by induced antigen-specific CD4+ regulatory T ... Gershon, R. K.; Kondo, K. (May 1970). "Cell interactions in the induction of tolerance: the role of thymic lymphocytes". ...
Removal of sialic acid residues from the surface of tumor cells makes them available to NK cells and cytotoxic T lymphocytes ... Below is a table that listed known PRRs and interferon regulatory factors that are getting activated upon SeV infection. SeV ... Barnes BJ, Moore PA, Pitha PM (June 2001). "Virus-specific activation of a novel interferon regulatory factor, IRF-5, results ... The persistent infection can also be established instantly in interferon regulatory factor 3 (IRF-3)-knockdown cells. IRF-3 is ...
"IRF8 interferon regulatory factor 8 [Homo sapiens (human)] - Gene - NCBI". "MAP2K1 mitogen-activated protein kinase kinase 1 [ ... Shukla V, Lu R (August 2014). "IRF4 and IRF8: Governing the virtues of B Lymphocytes". Frontiers in Biology. 9 (4): 269-282. ... Follicular lymphoma (FL) is a cancer that involves certain types of white blood cells known as lymphocytes. The cancer ... These cells normally occupy the follicles (nodular swirls of various types of lymphocytes) in the germinal centers of lymphoid ...
Regulatory macrophages produce Interleukin 10, which can inhibit cytotoxic responses of other lymphocytes to cancer cell ... or regulatory. Regulatory-phenotype macrophages have only recently been recognized as an important contributor to tissue ... Regulatory macrophages do not fit into the M1/M2 classification system, and they display different markers. After receiving ... Similar molecules may cause development of an inhibitory, regulatory phenotype. A MAF can also alter the ability of macrophages ...
"Human lymphocytes interact directly with CD47 through a novel member of the signal regulatory protein (SIRP) family". J. ... Signal-regulatory protein gamma is a protein that in humans is encoded by the SIRPG gene. SIRPG has also recently been ... PDBe-KB provides an overview of all the structure information available in the PDB for Human Signal-regulatory protein gamma ( ... "Entrez Gene: SIRPG signal-regulatory protein gamma". Kharitonenkov A, Chen Z, Sures I, et al. (1997). "A family of proteins ...
"Induction of antigen-specific regulatory T lymphocytes by human dendritic cells expressing the glucocorticoid-induced leucine ... protects T lymphocytes from interleukin-2 withdrawal-induced apoptosis". Blood. 104 (1): 215-23. doi:10.1182/blood-2003-12-4295 ...
... on T lymphocytes: activation-dependent up-regulation and regulatory function". Eur. J. Immunol. 31 (4): 1173-80. doi:10.1002/ ... Together, CR3 and CR4 are involved in various functions of the T and B lymphocytes and NK cells. For instance, while both CR3 ... is a human cell surface receptor found on B and T lymphocytes, polymorphonuclear leukocytes (mostly neutrophils), NK cells, and ...
Many regulatory processes can lead to allelic exclusion. In one instance, one allele of the gene can become transcriptionally ... This phenomenon is most notable for playing a role in the development of B lymphocytes, where allelic exclusion allows for each ... This is significant as the co-expression of both alleles in B lymphocytes is associated with autoimmunity and the production of ... mature B lymphocyte to express only one type of immunoglobulin. This subsequently results in each B lymphocyte being able to ...
Li N, Workman CJ, Martin SM, Vignali DA (Dec 2004). "Biochemical analysis of the regulatory T cell protein lymphocyte ... Maçon-Lemaître L, Triebel F (Jun 2005). "The negative regulatory function of the lymphocyte-activation gene-3 co-receptor ( ... molecular analysis of the negative regulatory function of lymphocyte activation gene-3". Journal of Immunology. 169 (10): 5392- ... "T Lymphocytes infiltrating various tumour types express the MHC class II ligand lymphocyte activation gene-3 (LAG-3): role of ...
Moreno CS, Rogers EM, Brown JA, Boss JM (Jun 1997). "Regulatory factor X, a bare lymphocyte syndrome transcription factor, is a ... "Mutations in the bare lymphocyte syndrome define critical steps in the assembly of the regulatory factor X complex". Molecular ... "Entrez Gene: RFX5 regulatory factor X, 5 (influences HLA class II expression)". Hake SB, Masternak K, Kammerbauer C, Janzen C, ... Steimle V, Durand B, Barras E, Zufferey M, Hadam MR, Mach B, Reith W (May 1995). "A novel DNA-binding regulatory factor is ...
NKT cell Journal Screening Nature glossary on murine NKT cells Nature Reviews Web Focus on regulatory lymphocytes. ... While iNKT cells are not very numerous, their unique properties makes them an important regulatory cell that can influence how ... In addition there are subtypes specialized in T follicular helper-like function and IL-10 dependent regulatory functions. Once ... They engage in cross talk with other immune cells, like dendritic cells, neutrophils and lymphocytes. Activation occurs by ...
"Purified Bovine NF-κB Recognizes Regulatory Sequences in Multiple Genes Expressed During Activation of T- and B-Lymphocytes". ... bovine NF-kappa B recognizes regulatory sequences in multiple genes expressed during the activation of T and B lymphocytes. In ...
Testa U, Kühn L, Petrini M, Quaranta MT, Pelosi E, Peschle C (July 1991). "Differential regulation of iron regulatory element- ... binding protein(s) in cell extracts of activated lymphocytes versus monocytes-macrophages". The Journal of Biological Chemistry ...
"MTG8 proto-oncoprotein interacts with the regulatory subunit of type II cyclic AMP-dependent protein kinase in lymphocytes". ...
"MTG8 proto-oncoprotein interacts with the regulatory subunit of type II cyclic AMP-dependent protein kinase in lymphocytes". ... Four different regulatory subunits and three catalytic subunits of PKA have been identified in humans. The protein encoded by ... Oyen O, Myklebust F, Scott JD, Hansson V, Jahnsen T (Mar 1989). "Human testis cDNA for the regulatory subunit RII alpha of cAMP ... cAMP-dependent protein kinase type II-alpha regulatory subunit is an enzyme that in humans is encoded by the PRKAR2A gene. cAMP ...
"Expanded Autologous Regulatory T-lymphocyte Infusions in ALS: A Phase I, First-In-Human Study". Neurology(R) Neuroimmunology & ... She found that infusion of autologous regulatory T cells in patients with ALS slowed the progression of disease. Cudkowicz has ...
... pro-regulatory cytokine, has also been implicated.[citation needed] In immunocompetent patients, Epstein-Barr virus can cause ... the lack of T-cell immunosurveillance can lead to the proliferation of these EBV-infected B-lymphocytes.[citation needed] ... The disease is an uncontrolled proliferation of B cell lymphocytes latently infected with Epstein-Barr virus (EBV). Production ...
... lymphocyte function-associated antigen). It elicits shedding of CD23. It downregulates the B cell receptor. It induces ... Rituximab has a general regulatory effect on the cell cycle. Preferential elimination of malignant B cells with high CD20 ... and lymphocyte predominant subtype, of Hodgkin's Lymphoma. This also includes Waldenström's macroglobulinemia, a type of NHL. ... "B-Lymphocyte Depletion in Patients With Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Randomized, Double-Blind, Placebo ...
Common variable immunodeficiency is thought to be due to a problem in the differentiation from lymphocytes to plasma cells. The ... Helper CD4+ / TFH / Th3 / Th17 / Regulatory). *γδ ... Plasma cells are large lymphocytes with a considerable nucleus- ...
T细胞(英語:T cell、T lymphocyte)是淋巴细胞的一种,在免疫反應中扮演着重要的角色。T是胸腺(thymus)而不是甲狀腺(thyroid)的英文缩写。T细胞在骨髓被製造出來之後,在胸腺内進行「新兵訓練」分化成熟為不同亚型的效应T細胞,成 ... Role of regulatory T cells during virus infection. Immunological Reviews. September 2013, 255 (1): 182-96. PMC 3748387. PMID ... Regulatory T cells: recommendations to simplify the nomenclature. Nature Immunology. 2013-04, 14 (4):
... such as lymphocytes, also undergo programmed cell death leading to an abnormally low concentration of lymphocytes in the blood. ... proteins including interferon regulatory factor 3 and interferon regulatory factor 7 trigger a signalling cascade that leads to ...
... has a general regulatory effect on the cell cycle.. *It increases MHC II and adhesion molecules LFA-1 and LFA-3 ( ... "B-Lymphocyte Depletion in Patients With Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Randomized, Double-Blind, Placebo ... including non-Hodgkin's lymphoma and lymphocyte predominant subtype, of Hodgkin's Lymphoma.[12] This also includes ...
"Human cord blood stem cell-modulated regulatory T lymphocytes reverse the autoimmune-caused type 1 diabetes in nonobese ...
In common with other steroid receptors, the progesterone receptor has a N-terminal regulatory domain, a DNA binding domain, a ... "No evidence for the expression of the progesterone receptor on peripheral blood lymphocytes during pregnancy". Human ... transcriptional activator activity, RNA polymerase II transcription regulatory region sequence-specific binding. ...
T細胞(英語:T cell、T淋巴細胞/T lymphocyte)是淋巴細胞的一種,在免疫反應中扮演着重要的角色。T細胞在胸腺內分化成熟,成熟後移居於周圍淋巴組織中。T是「胸腺」(thymus)而不
... gene transcription is controlled by multiple gene regulatory proteins such as transcription factors which bind to ... "RNA synthesis and histone acetylation during the course of gene activation in lymphocytes". Proceedings of the National ... the condensed chromosomes are assembled through interactions between nucleosomes and other regulatory proteins. ... This shows an important regulatory link between cell-cycle control and histone synthesis. ...
T cells (T lymphocytes) - T lymphocyte proliferation assay - T lymphocytes - T suppressor cells - T4 cell - T4 cells (T-helper ... regulatory genes - regulatory T cells - remission - renal - rescue therapy - resistance - retina - retinal detachment - ... B-cell lymphoma - B cells - B lymphocytes (B cells) - bactericidal - bacteriostatic - bacterium - baculovirus - baseline - ... lymphocyte - lymphoid interstitial pneumonitis (LIP) - lymphoid organs - lymphoid tissue - lymphokine-activated killer cells ( ...
Lymphocyte. Main article: Lymphocyte. Lymphocytes are much more common in the lymphatic system than in blood. Lymphocytes are ... Regulatory (suppressor) T cells: Returns the functioning of the immune system to normal operation after infection; prevents ... Lymphocyte. 30%. Small lymphocytes 7-8. Large lymphocytes 12-15. *B cells: releases antibodies and assists activation of T ... lymphocytes) by hematopoietic lineage (cellular differentiation lineage).[6] Lymphocytes can be further classified as T cells, ...
The promoter of the provirus DNA can also cause over expression of regulatory genes. ... "Lymphocyte T-cell immunomodulator (LTCI): Review of the immunopharmacology of a new biologic" (PDF). Intern J Appl Res Vet Med ...
Astrin SM, Laurence J (1992). "Human immunodeficiency virus activates c-myc and Epstein-Barr virus in human B lymphocytes". Ann ... chromosome translocation in a human leukemia T-cell line indicates that putative regulatory regions are not altered". Proc. ... "MYC oncogene involved in a t(8;22) chromosome translocation is not altered in its putative regulatory regions". Proc. Natl. ...
Ley K, Smith E, Stark MA (2006). "IL-17A-producing neutrophil-regulatory Tn lymphocytes". Immunol. Res. 34 (3): 229-42. PMID ... "Selective regulatory function of Socs3 in the formation of IL-17-secreting T cells". Proc. Natl. Acad. Sci. U.S.A. 103 (21): ... "Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells". Nature 441 (7090): ...
The activity of this kinase is restricted to the G1-S phase, which is controlled by the regulatory subunits D-type cyclins and ... 1995). "A p16INK4a-insensitive CDK4 mutant targeted by cytolytic T lymphocytes in a human melanoma". Science. 269 (5228): 1281- ... Serrano M, Hannon GJ, Beach D (1994). "A new regulatory motif in cell-cycle control causing specific inhibition of cyclin D/ ...
transcription regulatory region DNA binding. • protein binding. • protease binding. • tumor necrosis factor receptor binding. • ... In 1968, Gale A Granger from the University of California, Irvine, reported a cytotoxic factor produced by lymphocytes and ... One explanation for a possible mechanism is this observation that TNF has a positive effect on regulatory T cells (Tregs), due ... although it can be produced by many other cell types such as CD4+ lymphocytes, NK cells, neutrophils, mast cells, eosinophils, ...
These are compatible with regulation relevant to lymphocytes and deregulation in cancer. ... "Connecting the dots: potential of data integration to identify regulatory SNPs in late-onset Alzheimer's disease GWAS findings ...
The T-cell receptor, or TCR, is a molecule found on the surface of T cells, or T lymphocytes,[1] that is responsible for ... On helper T cells and regulatory T cells, this co-receptor is CD4 that is specific for MHC class II. ... 2001). Immunobiology: The Immune System in Health and Disease (5th ed.). Chapter 4, The Generation of Lymphocyte Antigen ... When the TCR engages with antigenic peptide and MHC (peptide/MHC), the T lymphocyte is activated through signal transduction, ...
ஒழுங்குபடுத்தும் டி உயிரணுக்கள் (Regulatory (suppressor) T cells): தொற்று நீங்கியதும் நோய் எதிர்ப்பாற்றல் முறைமையின் ... நிணநீர் செல்கள் (Lymphocytes). *ஒற்றைக் குழியம் (Monocyte). *பெருவிழுங்கி (Macrophage). *கிளையி உயிரணுக்கள் (Dendritic cell) ...
This effort was accompanied by local governmental and supragovernmental regulatory bodies' requirements to better characterize ... as well as increasing the proportion of T lymphocytes and natural killer cells.[96][97] LAB products might aid in the treatment ... but no standard in medical practice or regulatory approval exists for such treatment.[94] The only peer-reviewed treatments for ... few have been sufficiently developed in basic and clinical research to warrant approval for health claim status by a regulatory ...
Nucleosome position is not random, and determine the accessibility of DNA to regulatory proteins. This determines differences ... "Soy isoflavone supplementation in healthy men prevents NF-kappa B activation by TNF-alpha in blood lymphocytes". Free Radic. ...
For their discovery of the two distinct classes of lymphocytes, B and T cells - a monumental achievement that provided the ... For discoveries concerning the molecular machinery and regulatory mechanism that underlie the rapid release of ...
PSGL-1 is situated on various hematopoietic cells such as neutrophils, eosinophils, lymphocytes, and monocytes, in which it ... same as complement regulatory proteins: CRP) having short consensus repeats (~60 amino acids). The number of CRP repeats is the ...
Many cells of the immune system are required for this process, including lymphocytes (T-cells and B-cells) and antigen ... The 60kDa DNA/RNA binding protein and 52kDa T-cell regulatory protein are the best characterised antigens of anti-Ro antibodies ... In normal physiology, lymphocytes that recognise human proteins (autoantigens) either undergo programmed cell death (apoptosis ... This self-tolerance means that lymphocytes should not incite an immune response against human cellular antigens. Sometimes, ...
"Single-cell RNA sequencing reveals intrinsic and extrinsic regulatory heterogeneity in yeast responding to stress". PLOS ... "High-throughput targeted long-read single cell sequencing reveals the clonal and transcriptional landscape of lymphocytes" ...
A lymphoblast is a modified naive lymphocyte with altered cell morphology. It occurs when the lymphocyte is activated by an ... Helper CD4+ / TFH / Th3 / Th17 / Regulatory). *γδ ... Lymphoblasts look like immature lymphocytes, and were once ... Lymphoblasts can also refer to immature cells which typically differentiate to form mature lymphocytes.[2] Normally ... The Chronic Lymphocytic Leukemia Research Consortium defines a lymphoblast as "A lymphocyte that has become larger after being ...
Suppressor population or Regulatory T cell theory, wherein regulatory T-lymphocytes (commonly CD4+FoxP3+ cells, among others) ... The roles of specialized immunoregulatory cell types, such as regulatory T cells, NKT cells, γδ T-cells in the pathogenesis of ... Dendritic cell apoptosis - immune system cells called dendritic cells present antigens to active lymphocytes. Dendritic cells ... In this form of the disease, the absence of lymphocytes can accelerate organ damage, and intravenous IgG administration can be ...
... especially lymphocytes), chemotherapy drugs often find use in a host of diseases that result from harmful overactivity of the ... effects on immuno-regulatory cyclooxygenase-2 enzyme pathways; reduction in pro-inflammatory cytokines; and anti-proliferative ...
Neutrophils, monocytes, macrophages, dendritic cells, CD4+ T cells, and B cells all undergo apoptosis, whereas regulatory T ... of the lymphocytes, possibly with a toxic effect on mitochondrial function.[47] Although etomidate has a minimal effect on the ...
Astrin SM, Laurence J, Human immunodeficiency virus activates c-myc and Epstein-Barr virus in human B lymphocytes, in Ann. N. Y ... chromosome translocation is not altered in its putative regulatory regions (PDF), in Proc. Natl. Acad. Sci. U.S.A., vol. 84, nº ... the center stage of a novel transcription factors regulatory pathway? (PDF), in Oncogene, vol. 19, nº 29, luglio 2000, pp. 3266 ... chromosome translocation in a human leukemia T-cell line indicates that putative regulatory regions are not altered (PDF), in ...
Opinion-regulatory lymphocytes: natural versus adaptive regulatory T cells. Nat Rev Immunol 2003;3:253-257. ... Regulatory lymphocytes: antigen-induced regulatory T cells in autoimmunity. Nat Rev Immunol 2003;3:223-232. ... Regulatory T-lymphocytes in asthma. A. J. M. van Oosterhout, N. Bloksma ... The adaptive T-regulatory cells are further subdivided into T-regulatory cells type 1 and T-helper cell type 3 that mediate ...
Regulatory T Lymphocytes in Periodontitis: A Translational View. by Mediators of Inflammation; Biological sciences B cells ... APA style: Regulatory T Lymphocytes in Periodontitis: A Translational View.. (n.d.) >The Free Library. (2014). Retrieved Aug 11 ... MLA style: "Regulatory T Lymphocytes in Periodontitis: A Translational View.." The Free Library. 2018 Hindawi Limited 11 Aug. ... ...
Regulatory T-cell response and tumor vaccine-induced cytotoxic T lymphocytes in human melanoma.. Chakraborty NG1, Chattopadhyay ... The understanding of these T-regulatory (T-reg) cells in the generation of antitumor cytolytic T lymphocyte (CTL) response is ... Analysis of postvaccine peripheral blood lymphocytes (PBL) from patients showed an increased amount of interleukin (IL)-10 ...
Proper TCR signaling requires the sequential activities of lymphocyte-specific protein tyrosine kinase (Lck) and zeta-chain- ... Activation of T lymphocytes constitutes a central event in adaptive immune responses against infectious pathogens or tumor ... Review and Case Reports focusing on the regulatory mechanisms of early intracellular signaling in T lymphocytes. ... Keywords: TCR, T lymphocytes, T cell activation, Thymic Development, Adaptor Proteins Important Note: All contributions to this ...
Functional Role of Regulatory Lymphocytes in Stroke. Facts and Controversies. Arthur Liesz, Xiaoming Hu, Christoph Kleinschnitz ...
Rel Induces Interferon Regulatory Factor 4 (IRF-4) Expression in Lymphocytes. Raelene J. Grumont, Steve Gerondakis ... 1989) Contingent genetic regulatory events in T lymphocyte activation. Science 243:355-361, pmid:2783497. ... Purification of Primary B and T Lymphocytes.. Small resting B and T lymphocytes were purified from the spleens of 6-8-wk-old ... a lymphoid-specific IFN regulatory factor is directly induced by Rel in activated lymphocytes and that an absence of Rel ...
Regulatory T-lymphocytes mediate amyotrophic lateral sclerosis progression and survival.. Henkel JS1, Beers DR, Wen S, Rivera ... CD4+CD25High regulatory T-lymphocytes (Tregs) are reduced in rapidly progressing ALS patients ... In amyotrophic lateral sclerosis (ALS) mice, regulatory T-lymphocytes (Tregs) are neuroprotective, slowing disease progression ... Collectively, these data suggest that Tregs and Th2 lymphocytes influence disease progression rates. Importantly, early reduced ...
Intraepithelial CD8+ tumor-infiltrating lymphocytes and a high CD8+/regulatory T cell ratio are associated with favorable ... Intraepithelial CD8+ tumor-infiltrating lymphocytes and a high CD8+/regulatory T cell ratio are associated with favorable ... Intraepithelial CD8+ tumor-infiltrating lymphocytes and a high CD8+/regulatory T cell ratio are associated with favorable ... Intraepithelial CD8+ tumor-infiltrating lymphocytes and a high CD8+/regulatory T cell ratio are associated with favorable ...
The protein and mRNA expression level of IL-38, periostin, peripheral CD4+CD25+CD134+ T lymphocytes as well as CD4+ ... Treg lymphocytes were markedly decreased in asthmatic patients with and without steroid treatment than those in controls (all p ... CD134+ activated T lymphocytes was also significantly higher in asthmatic patients with steroid treatment than those in ... 0.05). The elevated IL-38 concentration negatively correlated with the percentage of Treg lymphocytes in asthmatic patients ...
The Influence of the Regulatory T Lymphocytes on Atherosclerosis. Israel Gotsman, Rajat Gupta, Andrew H. Lichtman ... A well adapted regulatory contrivance: regulatory T cell development and the forkhead family transcription factor Foxp3. Nat ... Adoptive transfer of Treg-deficient lymphocytes and Treg cells from db/db mice into Apoe−/−/Rag2−/− recipients caused a greater ... Yang K, Li D, Luo M, Hu Y. Generation of HSP60-specific regulatory T cell and effect on atherosclerosis. Cell Immunol. 2006; ...
T regulatory lymphocytes were shown to be partly responsible for immune tolerance to cancer cells. In that respect these cells ... purification of regulatory T cells on the one hand and T lymphocytes depleted from. regulatory T cells (effectors T-cells) on ... selectively depleting regulatory T-cell during a controlled amount of time. This strategy. will be tested in patients with ... Controlled and Selective Depletion of Regulatory T-cell for Cancer Treatment, Efficacy and Safety Study. Trial Phase:. Phase 1/ ...
CD4+CD25+ Regulatory Lymphocytes Require Interleukin 10 to Interrupt Colon Carcinogenesis in Mice Susan E. Erdman, Varada P. ... CD4+CD25+ Regulatory Lymphocytes Require Interleukin 10 to Interrupt Colon Carcinogenesis in Mice ... CD4+CD25+ Regulatory Lymphocytes Require Interleukin 10 to Interrupt Colon Carcinogenesis in Mice ... CD4+CD25+ Regulatory Lymphocytes Require Interleukin 10 to Interrupt Colon Carcinogenesis in Mice ...
The ratio of regulatory to effector T cells was higher in patients than that in controls, suggesting that T regulatory cells ... Our data suggest a defective activation of T regulatory cells in long-standing diabetics due to a lower expression of PD-1 on ... Percentages of total PD-1+, PD-1low and PD-1high expressing T regulatory cells did not change in patients and in controls. ... After stimulation, a defect in T regulatory cell proliferation was observed in diabetics and the percentages of total PD-1+, PD ...
Human lymphocytes, in particular T lymphocytes, carry β-adrenergic receptors (25, 33, 39). Administration of epinephrine and ... Cortisol-augmented CXCR4 expression on CD4, CD8 T lymphocytes.. CXCR4 expression on CD4 and CD8 T lymphocytes when incubated ... Cortisol-induced CXCR4 augmentation mobilizes T lymphocytes after acute physical stress. Mitsuharu Okutsu, Kenji Ishii, Kai Jun ... Short-term exposure to cortisol was sufficient to augment CXCR4 expression on CD4 and CD8 T lymphocytes.. It is well documented ...
Schulz Experimental and Mathematical Analysis of Regulatory Networks in T-helper Lymphocytes ... Experimental and Mathematical Analysis of Regulatory Networks in T-helper Lymphocytes Edda G. Schulz ISBN 978-3-8325-2498-2 170 ... In the first part, structure and function of the gene-regulatory network that controls differentiation of type I T-helper (Th1 ... a quantitative mathematical model of the NFAT regulatory network is developed and the underlying design principles are analyzed ...
Increased T-regulatory cells within lymphocyte follicles in moderate COPD. J. Plumb, L. J. C. Smyth, H. R. Adams, J. Vestbo, A. ... Increased T-regulatory cells within lymphocyte follicles in moderate COPD. J. Plumb, L. J. C. Smyth, H. R. Adams, J. Vestbo, A. ... Increased T-regulatory cells within lymphocyte follicles in moderate COPD. J. Plumb, L. J. C. Smyth, H. R. Adams, J. Vestbo, A. ... Increased T-regulatory cells within lymphocyte follicles in moderate COPD Message Subject (Your Name) has sent you a message ...
CD4+CD25+ T regulatory lymphocytes associate with CD8+CD28− T regulatory cells so that the immunosuppressive activity of tumor- ... 3 Abbreviations used in this paper: Treg, regulatory T lymphocyte; TIL, tumor-infiltrating lymphocyte. ... T lymphocytes were constituted by regulatory cells. Recently, Pages et al. (22) reported that CD8+CD28− T lymphocytes, ... T lymphocytes are a composite cell population including effector and regulatory lymphocytes and that prognosis likely ...
CD25+ T regulatory lymphocytes in mice infected with Toxoplasma gondii. T regulatory (Treg) cells have been shown to play an ... T regulatory cells have been shown to control the persistence of the protozoan parasite, Leishmania major, in mice; however, ... These cells are differentiated from other T lymphocyte populations based on the co-expression of CD4 and CD25 and expression of ... important role in our immune system in controlling the activity of other T lymphocytes. ...
Tumor-infiltrating regulatory T lymphocytes (Treg) can suppress effector T cells specific for tumor antigens. Deeper molecular ... Transcriptional Landscape of Human Tissue Lymphocytes Unveils Uniqueness of Tumor-Infiltrating T Regulatory Cells. De Simone, M ... "Transcriptional Landscape of Human Tissue Lymphocytes Unveils Uniqueness of Tumor-Infiltrating T Regulatory Cells" Immunity ( ... definitions of tumor-infiltrating-lymphocytes could thus offer therapeutic opportunities. Transcriptomes of T helper 1 (Th1), ...
Siponimod enriches regulatory T and B lymphocytes in secondary progressive multiple sclerosis. ... Siponimod enriches regulatory T and B lymphocytes in secondary progressive multiple sclerosis. ... and T regulatory cells (Tregs) were enriched. Transitional regulatory B cells (CD24hiCD38hi) and B1 cell subsets (CD43+CD27+) ... Flow cytometric analysis showed that within the remaining lymphocyte subsets there was a reduction in the frequencies of CD4+ ...
LASSO, Paola et al. Dendritic cells and natural regulatory T lymphocytes in chronic chagasic patients. Infect. [online]. 2009, ... CD123+ and natural regulatory T lymphocytes CD3+ CD4+ CD25+ Foxp3+ CD127low. Cellular proportions were calculated using the ... On the contrary, it was found that the proportion of natural regulatory T cells was significantly higher in chronic chagasic ... These results suggest that the higher proportion of natural regulatory T cells in chronic chagasic patients might contribute to ...
Generation of CD4+ or CD8+ regulatory T cells upon mesenchymal stem cell-lymphocyte interaction ... Generation of CD4+ or CD8+ regulatory T cells upon mesenchymal stem cell-lymphocyte interaction ... Generation of CD4+ or CD8+ regulatory T cells upon mesenchymal stem cell-lymphocyte interaction ...
Generation of CD4+ or CD8+ regulatory T cells upon mesenchymal stem cell-lymphocyte interaction ... Generation of CD4+ or CD8+ regulatory T cells upon mesenchymal stem cell-lymphocyte interaction ... Different subsets of Regc inhibit lymphocyte proliferation. A. Highly purified CD25− or CD4+ or CD8+ lymphocytes were cultured ... Generation of CD4+ or CD8+ regulatory T cells upon mesenchymal stem cell-lymphocyte interaction ...
B and NK lymphocytes. Contact-dependent suppression mechanisms have been well-studied, though contact-independent Treg activity ... Regulatory T cells (Tregs) play a fundamental role in the maintenance of immunological tolerance by suppressing effector target ... Contact-independent suppressive activity of regulatory T cells is associated with telomerase inhibition, telomere shortening ... and target lymphocyte apoptosis.. [Dmitry D Zhdanov, Yulia A Gladilina, Dmitry V Grishin, Vladimir A Grachev, Valentina S ...
Telomerase Mediates Lymphocyte Proliferation but Not the Atherosclerosis-Suppressive Potential of Regulatory T-Cells. Gavin ... Telomerase Mediates Lymphocyte Proliferation but Not the Atherosclerosis-Suppressive Potential of Regulatory T-Cells ... Telomerase Mediates Lymphocyte Proliferation but Not the Atherosclerosis-Suppressive Potential of Regulatory T-Cells ... Telomerase Mediates Lymphocyte Proliferation but Not the Atherosclerosis-Suppressive Potential of Regulatory T-Cells ...
2000) Cytotoxic T lymphocyte-associated antigen 4 plays an essential role in the function of CD25+CD4+ regulatory cells that ... Immunologic Self-Tolerance Maintained by Cd25+Cd4+Regulatory T Cells Constitutively Expressing Cytotoxic T Lymphocyte- ... Immunologic Self-Tolerance Maintained by Cd25+Cd4+Regulatory T Cells Constitutively Expressing Cytotoxic T Lymphocyte- ... regulatory T cells; i.e., costimulation via CTLA-4 may activate the regulatory T cells to exert suppression, whereas ...
ALS patients regulatory T lymphocytes are dysfunctional, and correlate with disease progression rate and severity. ... ALS patients regulatory T lymphocytes are dysfunctional, and correlate with disease progression rate and severity. ... In ALS mouse models, decreased regulatory T lymphocytes (Tregs) exacerbate the neuroinflammatory process, leading to ... To address this question, T lymphocyte proliferation assays were performed. Compared with control Tregs, ALS Tregs were less ...
Increased Populations of Regulatory T Cells in Peripheral Blood and Tumor-Infiltrating Lymphocytes in Patients with Gastric and ... Increased Populations of Regulatory T Cells in Peripheral Blood and Tumor-Infiltrating Lymphocytes in Patients with Gastric and ... Increased Populations of Regulatory T Cells in Peripheral Blood and Tumor-Infiltrating Lymphocytes in Patients with Gastric and ... Increased Populations of Regulatory T Cells in Peripheral Blood and Tumor-Infiltrating Lymphocytes in Patients with Gastric and ...
Prevention of acute and chronic allograft rejection with CD4+CD25+Foxp3+ regulatory T lymphocytes. Nat. Med. 14, 88-92 (2008). ... CD4+CD25+ Regulatory T Cell Depletion Improves the Graft-Versus-Tumor Effect of Donor Lymphocytes After Allogeneic ... CD4+CD25+ Regulatory T Cell Depletion Improves the Graft-Versus-Tumor Effect of Donor Lymphocytes After Allogeneic ... CD4+CD25+ Regulatory T Cell Depletion Improves the Graft-Versus-Tumor Effect of Donor Lymphocytes After Allogeneic ...
We have previously demonstrated that CD4+ CD25+ natural regulatory T cells (Treg cells) induce down-modulation of CD80 and CD86 ... T lymphocyte antigen-4-dependent down-modulation of costimulatory molecules on dendritic cells in CD4+ CD25+ regulatory T-cell- ... We have previously demonstrated that CD4+ CD25+ natural regulatory T cells (Treg cells) induce down-modulation of CD80 and CD86 ... Further, we report that down-modulation was induced rapidly and was inhibited by blocking cytotoxic T lymphocyte antigen-4 ( ...
  • In recent years, the general knowledge regarding the regulation of infectious, autoimmune diseases, asthma and allergen immunotherapy by T-regulatory (Treg) cells, has rapidly increased. (
  • At present, naturally occurring and adaptive T-regulatory cells (Treg) cells (nTreg and aTreg, respectively) are taking the centre stage as the crucial immunoregulatory cells that are capable of suppressing Th1- and Th2-mediated adaptive immune responses in a cell contact-dependant fashion directly or by acting on APCs. (
  • Major characteristics of subsets of CD4+ T-regulatory (Treg) cells based on cell-surface markers, immunosuppressive cytokine secretion and suppressive action. (
  • Although different T cell types with regulatory functions have been identified, the most physiologically relevant Treg population is characterized as [CD4.sup. (
  • To address whether Tregs and FoxP3, a transcription factor required for Treg function, similarly influence progression rates of ALS patients, T-lymphocytes from patients were assessed by flow cytometry. (
  • 7 ) reported that tumor infiltration by a subpopulation of CD3 + CD4 + T cells with immunosuppressive properties (suppressor or regulatory T cells, Treg) predicted reduced survival in EOC. (
  • We investigated the expression of novel anti-inflammatory interleukin (IL)-38 and regulatory T (Treg) lymphocytes in childhood asthma patients. (
  • The protein and mRNA expression level of IL-38, periostin, peripheral CD4 + CD25 + CD134 + T lymphocytes as well as CD4 + CD25 high FoxP3 + and CD4 + CD25 high CD127 − Treg lymphocytes from 40 asthmatic patients and 20 normal control (NC) subjects were studied using ELISA, qPCR and flow cytometry. (
  • One of these mechanisms involves regulatory T cells (Treg) that actively suppress responses of effector T cells. (
  • 12 It is not yet clear whether these peripherally converted cells acquire the full marker and regulatory characteristics of natural Treg, but they have been shown to be induced subsequent to a variety of manipulations such as exposure to TGF-β and IL-2 during activation, or by exposure to peptide antigen. (
  • Among mechanisms responsible for tumor immune escape, great relevance is attributed to tumor infiltration by regulatory T lymphocytes (Treg), 3 based on the observation that these cells are present in tumor-infiltrating lymphocytes (TILs), inhibit antitumor immune responses and their rate of infiltration correlates with tumor progression ( 5 ). (
  • T regulatory (Treg) cells have been shown to play an important role in our immune system in controlling the activity of other T lymphocytes. (
  • Tumor-infiltrating regulatory T lymphocytes (Treg) can suppress effector T cells specific for tumor antigens. (
  • B ) Tregs from patients with slowly progressing ALS and the control individuals are more suppressive than patients with rapidly progressing ALS across all responder T lymphocyte/Treg suppression assay ratios (CD4 + CD25 - /CD4 + CD25 hi ). (
  • We have previously demonstrated that CD4+ CD25+ natural regulatory T cells (Treg cells) induce down-modulation of CD80 and CD86 (B7) molecules on dendritic cells (DCs) in vitro. (
  • Further, we report that down-modulation was induced rapidly and was inhibited by blocking cytotoxic T lymphocyte antigen-4 (CTLA-4), which is constitutively expressed by the Treg cells. (
  • Methods Flow cytometry was used before and after respectively to detect the peripheral blood T lymphocyte subsets( CD3~+,CD4~+,CD8~+,CD4~+/ CD8~+,CD4~+CD25~+Treg) and their levels in 30 patients with invalid red blood cell infusion. (
  • In the successful transfusion group,the level of T lymphocyte subsets did not change before and after blood transfusion( CD3~+,CD4~+,CD8~+,CD4~+/ CD8~+,CD4~+CD25~+Treg)( P 0. (
  • Here we provide a description of lymphocyte populations in human lymph nodes (LN) with a special emphasis on the CD4+ lymphocyte population constitutively expressing CD25 at a high level and endowed with immunoregulatory properties [T regulatory (Treg) cells]. (
  • There has been renewed interest in regulatory T (Treg) cells over the last 10 years and in the role they play in modulating immune responses to self and foreign antigens. (
  • Regulatory T cells are a heterogeneous group of cells, including CD4+ CD25+ (Treg) T cells, Tr1 and Th3 regulatory T cells ( 1 , 2 ) and CD8+ regulatory T cells ( 3 ). (
  • The CD4+ CD25+ Treg cells are currently the best defined and characterised among the various subgroups of regulatory T cells ( 4 ). (
  • FOXP3, a transcription factor whose expression confers the regulatory phenotype on both murine and human T cells, is now thought to represent the most specific Treg cell marker ( 9 - 12 ). (
  • CD4+ effector T cells can be further divided into proinflammatory Th1, Th17, and anti-inflammatory Th2 and Foxp3+ regulatory T cell (Treg) subtypes based on their functionality and cytokine production [ 12 ]. (
  • The expression of FoxP3, a critical transcription factor required for Treg function, and Gata3, a transcription factor for Th2 lymphocytes, are reduced rapidly progressing patients. (
  • Moreover, C3 −/− allografts caused attenuated Th1/Th17 responses, but increased CD4 + CD25 + Foxp3 + regulatory T (Treg) cell expression markedly in local intragraft and H-2 bm12 recipients. (
  • This hypothesis is supported by our preliminary data demonstrating that controlled release of Treg recruiting factors leads to an increase in regulatory T-cells in the periodontium, in the draining lymph nodes, and, consequently, resolution of periodontal disease symptoms 2 mouse models. (
  • In the last few years, some translational studies in patients with breast carcinoma have suggested that infiltration by tumor infiltrating lymphocytes (TIL) and regulatory T (Treg) cells might have a great significance in the final clinical outcomes. (
  • Regulatory T (Treg) cells may participate in mediating a suppressive microenvironment in tumor tissue and contribute to tumor evasion from immune response. (
  • Study suggests that Treg lymphocytes were increased in ascites and peripheral blood in EOC patients and could be associated with diminished overall survival, via impairment antitumor immune response. (
  • In recent years, regulatory T (Treg) lymphocytes that constitutively express CD4 and the Interleukin-2 receptor-α chain (CD25) have been shown to modulate the inflammatory response to infection and prevent autoimmune disease. (
  • Expression of the FOXP3 gene has to date been found universally in rodent and human Treg cells and it is suggested that FOXP3 confers these cells with regulatory properties. (
  • However, rapidly proliferating effector T-cells also rely on aerobic glycolysis, whereas regulatory T-cells (Treg) do not. (
  • The effect of DCA on glucose metabolism and Treg differentiation was evaluated in alloreactive lymphocytes. (
  • Conclusions: DCA inhibits aerobic glycolysis and induces Treg differentiation in human alloreactive lymphocytes. (
  • The neurotransmitter dopamine (DA) has prominent effects in the immune system and between the immune cells, CD4 + regulatory T (Treg) lymphocytes, a specialized T-cell subset crucial for the control of immune homeostasis, are especially sensitive to DA. (
  • Dopaminergic receptor (DR) gene polymorphisms affect cAMP responses in peripheral blood mononuclear cells (PBMC) and regulatory T (Treg) cell‐induced inhibition of effector T (Teff) cell proliferation. (
  • Background The removal of human regulatory T (Treg) cells from a cellular product prior to the induction of a T-cell response has the potential to boost the total yield of antigen (Ag)-specific CD4+ and CD8+ T cells. (
  • Krasimirova E, Velikova T, Ivanova-Todorova E, Tumangelova-Yuzeir K, Kalinova D, Boyadzhieva V, Stoilov N, Yoneva T, Rashkov R, Kyurkchiev D. Treg/Th17 cell balance and phytohaemagglutinin activation of T lymphocytes in peripheral blood of systemic sclerosis patients. (
  • T lymphocytes that constitutively express the IL-2 receptor a-chain, CD25, and the transcription factor Foxp3, comprising approximately 10% of the [CD4.sup. (
  • At the terminal stage of differentiation, the transcription factor Foxp3 is upregulated by the action of IL-2 through CD25, whose signalization induces further CD25 production and high expression of suppressor genes, rendering regulatory functions [7]. (
  • Furthermore, reduction in atherosclerosis in ApoE −/− mice has also been achieved through adoptive transfer of CD4 + CD25 + regulatory T cells. (
  • Animal models suggested that a CD4 + CD25 + population has a regulatory function capable of preventing activation and effector functions of autoreactive T cells. (
  • CD4 + CD25 + T regulatory lymphocytes associate with CD8 + CD28 − T regulatory cells so that the immunosuppressive activity of tumor-infiltrating regulatory T cell subsets, altogether considered, may become predominant. (
  • These cells are differentiated from other T lymphocyte populations based on the co-expression of CD4 and CD25 and expression of the Foxp3 gene. (
  • D. The expression of forkhead box p3 (Foxp3) mRNA was analyzed in PBMC or CD25 − PBMC alone or co-cultured with MSC (MSC-PBMC, MSC-CD25 − PBMC) or PHA blasts or CD4 + Reg c or CD8 + Reg c lymphocyte populations and expressed as change in fold increase, relative to the level of RNA polymerase II subunit A, using quantitative real-time PCR. (
  • CD28-deficient CD25 + CD4 + T cells can also suppress normal T cells, indicating that CD28 is dispensable for activation of the regulatory T cells. (
  • Thus, the CD25 + CD4 + regulatory T cell population engaged in dominant self-tolerance may require CTLA-4 but not CD28 as a costimulatory molecule for its functional activation. (
  • Here, we demonstrate that CTLA-4 is indeed a key costimulatory molecule for activating CD25 + CD4 + regulatory T cells to exert suppression and thereby to control self-reactive T cells, and that in vivo blockade of CTLA-4 expressed on the regulatory T cells suffices to break natural self-tolerance and elicit pathological autoimmunity. (
  • Regulatory T cells (T-regs), characterized by coexpression of CD4 and CD25 markers, can inhibit the immune response mediated by CD4+/CD25− and CD8+ T cells. (
  • OBJECTIVE To investigate the proportional changes of CD4(+)CD25(+) regulatory T cells in peripheral blood after lymphocyte therapy in unexplained recurrent spontaneous abortion (URSA) patients. (
  • INTERVENTION(S) Measurements of CD4(+)CD25(+) regulatory T cells in peripheral blood before and after paternal or third-party lymphocyte immunization. (
  • Combination of CD4(+)CD25(+)CD127(-) regulatory T cells with MLC-BE and BE-Ab2: an efficient evaluation of the therapy of paternal lymphocyte induced immunization in unexplained recurrent spontaneous abortion patients. (
  • Regulatory T cells from colorectal cancer patients were FOXP3 positive and suppressed the proliferation of autologous CD4+ CD25- cells. (
  • Prevention of allograft rejection by amplification of Foxp3(+)CD4(+)CD25(+) regulatory T cells. (
  • CD4 + CD25 bright Foxp3 + Tregs also suppress the generation of cytotoxic T lymphocytes specific for the Wilms tumor antigen 1, resulting in more than an 80% decrease in specific target cell lysis. (
  • Methods: The abilities of primary BDCA1 + or monocyte-derived DCs from HCV patients (HCV-DC) to stimulate CD4 + , CD4 + CD25 - , or different ratios of CD4 + CD25 + /CD4 + CD25 - T cells were evaluated in mixed lymphocyte reactions. (
  • CD4 + CD25 + FoxP3 + ), which limit proliferation of HCV-specific T lymphocytes. (
  • CD8 + lymphocyte p21 cip1 production in FIV + and FIV - cats following CD4 + CD25 + co-culture . (
  • Human CD4(+)CD25(+) cells: a naturally occurring population of regulatory T cells. (
  • CD4+CD25+T-regulatory lymphocytes control expansion of hepatitis virus specific CD8+T cells. (
  • Furthermore, flow cytometry demonstrated that HLILs contained large populations of both interleukin-10 (IL-10)-secreting T-regulatory 1 (Tr1) and CD4 + CD25 + regulatory T cells. (
  • T lymphocytes at the periphery, named induced or peripheral Tregs (iTregs or pTregs). (
  • In amyotrophic lateral sclerosis (ALS) mice, regulatory T-lymphocytes (Tregs) are neuroprotective, slowing disease progression. (
  • Collectively, these data suggest that Tregs and Th2 lymphocytes influence disease progression rates. (
  • Flow cytometric analysis showed that within the remaining lymphocyte subsets there was a reduction in the frequencies of CD4+ and CD8+ naive T cells and central memory cells, while T effector memory cells, antiinflammatory Th2, and T regulatory cells (Tregs) were enriched. (
  • Additionally, a positive correlation was found between Tregs and regulatory B cells in siponimod-treated participants.CONCLUSION The shift toward an antiinflammatory and suppressive homeostatic immune system may contribute to the clinical efficacy of siponimod in SPMS.TRIAL REGISTRATION NCT02330965. (
  • Regulatory T cells (Tregs) play a fundamental role in the maintenance of immunological tolerance by suppressing effector target T, B and NK lymphocytes. (
  • Compared with control Tregs, ALS Tregs were less effective in suppressing responder T lymphocyte proliferation. (
  • Changes of immune function relevant inflammatory factor of IL-6, TNF-α concentration, regulatory T cell (Tregs), T-lymphocyte subsets, CD4+T cell, CD8+T cell, Natural Killer cell (NK) percentage in vivo before and after treatment in two groups were detected and analysed. (
  • Our objective was to examine the prognostic impact of tumor-infiltrating FoxP3(+) regulatory T cells (Tregs) in relation to cytotoxic CD8(+) T lymphocytes in patients with colon carcinomas characterized by DNA mismatch repair (MMR) status who participated in adjuvant chemotherapy trials. (
  • In mSOD1 transgenic mice, regulatory T‐lymphocytes (Tregs) have a documented neuroprotective role slowing disease progression. (
  • Unlike MILs from normal bone marrow, myeloma MILs possess few regulatory T cells (Tregs) and demonstrate an interleukin-17 phenotype that enhances OC activation. (
  • 8 The non-tumor-bearing marrow also serves as a reservoir of regulatory T cells (Tregs). (
  • They also interact with several other immune cells and promote the production of regulatory T cells or Tregs. (
  • Under stringent autologous culture conditions without exogenous cytokines, mature moDCs expand regulatory T cells (Tregs) by an IDO-dependent mechanism. (
  • Although mature moDCs can generate Tregs by this IDO-dependent mechanism to limit otherwise unrestrained immune responses, inhibition of this counter-regulatory pathway should also prove useful in sustaining responses stimulated by DC-based immunotherapy. (
  • Regulatory T cells (Tregs) play a central role in tempering immunity and in maintaining immune homeostasis. (
  • Regulatory T cells (Tregs) are important for the induction and maintenance of peripheral tolerance therefore, they are key in preventing excessive immune responses and autoimmunity. (
  • Since the discovery in 1969 of the suppressor T cells ( 1 ), the regulatory T cells (Tregs) research field has undergone an incredible boom over the years. (
  • Furthermore, we will explore the expansion of local lymphocytes toward an enriched population of Tregs through controlled release of a combination of several key molecules. (
  • Regulatory T cells (Tregs) are critical to maintain the homeostasis of the organism, i. e. , to prevent (excessive) inflammatory reactions against self and nonself. (
  • The extent of therapy-induced tumor necrosis was linearly related to the natural logarithm of the ratio of intratumoral CD8 + effector T cells to FoxP3 + regulatory T cells (Tregs) in posttreatment biopsies. (
  • They have also revealed the operation of regulatory T cells in small clusters within lymph nodes where conventional autoreactive cells produce IL-2 in response to self-antigens and are then silenced by TCR and IL-2 feedback activation of the associated Tregs. (
  • We report that this intervention induces functional regulatory T lymphocytes (Tregs) in mouse lung experimentally inflamed by intratracheal administration of lipopolysaccharide (LPS). (
  • Transitional regulatory B cells (CD24hiCD38hi) and B1 cell subsets (CD43+CD27+) were enriched, shifting the balance in favor of regulatory B cells over memory B cells. (
  • Different subsets of Reg c inhibit lymphocyte proliferation. (
  • Objective To investigate the peripheral blood T lymphocyte subsets in invalid red blood cell transfusion cases and to observe regulatory T cells( T-reg cells) level changes. (
  • To explore influences of lenalidomide on multiple myeloma, inflammatory factor, regulatory T cell and T-lymphocyte subsets. (
  • T-lymphocyte infiltration into colon carcinomas can influence clinical outcome, and interactions among T cell subsets may be more informative than either subset alone. (
  • In this review, we summarize the main lymphocyte subsets controlling immune responsiveness in the gut and their mechanisms of control, which involve maintenance of intestinal barrier function and suppression of chronic inflammation. (
  • This study was undertaken to measure the expression and function of the coinhibitory receptors (co-IRs) programmed cell death 1 (PD-1), T cell immunoglobulin and ITIM domain (TIGIT), T cell immunoglobulin and mucin domain 3 (TIM-3), and lymphocyte activation gene 3 (LAG-3) in lymphocyte subsets from the peripheral blood of patients with SSc. (
  • 1 2 3 4 This population of lymphocytes consists mainly of two cell subsets, designated Th1 and Th2, that differ in their cytokine production and their immunologic function. (
  • 5 6 7 The participation of these two lymphocyte subsets in immunopathogenic processes has been examined in animal studies. (
  • Likewise, regulatory B cell subsets have also been demonstrated to inhibit Th1 responses through IL-10 production during chronic infectious diseases such as visceral leishmaniasis. (
  • In lymphocytes, the Rel transcription factor is essential in establishing a pattern of gene expression that promotes cell proliferation, survival, and differentiation. (
  • Like Rel, it also appears to be critical in lymphocyte proliferation, as IRF-4 −/− B and T cells respond poorly to mitogens ( 14 ) and deregulated overexpression of IRF-4 due to the translocation of the gene into the Ig CH locus occurs in a subset of human multiple myelomas ( 15 ). (
  • After stimulation, a defect in T regulatory cell proliferation was observed in diabetics and the percentages of total PD-1 + , PD-1 low and PD-1 high expressing cells were lower in patients. (
  • The unprecedented observation was made that CD8 + CD28 − T regulatory lymphocytes are almost constantly present and functional in human tumors, being able to inhibit both T cell proliferation and cytotoxicity. (
  • Cells generated from MSC-PBMC co-cultures (Reg c ) inhibit lymphocyte proliferation. (
  • To address this question, T lymphocyte proliferation assays were performed. (
  • Samples were analyzed for cell density by automated imaging capture and further characterized for functional lymphocyte properties by assessing the cell activation markers HLA-DR and CD45RO, the cell proliferation marker Ki67, and the regulatory T-cell marker FOXP3. (
  • LGG can also regulate the proliferation of T lymphocytes in the intestine of early weaned piglets at 30 days and 45 days increase the number of CD3 + CD4 + T lymphocytes. (
  • These cells demonstrated typical T regulatory properties, being both hyporesponsive to stimuli and suppressing proliferation of T effector cells in co-culture. (
  • Results: DCA had a minor effect on lymphocyte proliferation and cytotoxicity. (
  • Johnsen, HE, Madsen, M & Kristensen, T 1979, ' Lymphocyte subpopulations in man: suppression of PWM-induced B-cell proliferation by infectious mononucleosis T cells ', Scandinavian Journal of Immunology , vol. 10, no. 3, pp. 251-5. (
  • We demonstrated that MSC-EVs were incorporated by lymphocytes in vitro and decreased T cell proliferation and Th1 differentiation. (
  • Baseline tumor biopsies from 196 patients in the NEOZOTAC trial were analyzed for CD8 (cytotoxic T-cells), FoxP3 (regulatory T-cells), CD68 (macrophages), and HLA class I (HCA2/HC10) expression by immunohistochemistry and subsequently related to pCR and disease-free survival (DFS). (
  • FOXP3 is not involved in the regulatory mechanisms of these cells in preterm infants and thus is not essential for regulatory function in humans. (
  • Several attempts have been made to evaluate the prognostic significance of tumor-infiltrating lymphocytes (TILs) in human cancers, and pronounced lymphocytic infiltration has been shown to be a prognostic parameter for better survival ( 1 - 5 ). (
  • Infiltration by tumor infiltrating lymphocytes (TIL) and their subtypes, tumor-associated macrophages (TAM) and myeloid-derived suppressive cells (MDSC) seem bona fide prognostic and even predictive biomarkers, that will eventually be incorporated into diagnostic and therapeutic algorithms of breast cancer. (
  • however, in the last years evidence has emerged demonstrating the importance of tumor lymphocyte infiltration in the clinical evolution of many cancer types. (
  • Paired baseline and postdosing tumor biopsy specimens were prospectively collected from 19 patients with metastatic melanoma, including 3 patients with an objective tumor response, receiving the anti-CTLA4 antibody tremelimumab within a clinical trial with primary endpoint of quantitating CD8 + cytotoxic T-lymphocyte (CTL) infiltration in tumors. (
  • Valverde CV, Miguel KL, Sánchez-Villanueva JA, Lambert AL, Portilla TC, Prado MCA (2016) Infiltration of Regulatory T Lymphocytes Impair Clinical Outcome in Ovarian Cancer Patients. (
  • Activation of T lymphocytes constitutes a central event in adaptive immune responses against infectious pathogens or tumor cells. (
  • Proper TCR signaling requires the sequential activities of lymphocyte-specific protein tyrosine kinase (Lck) and zeta-chain-associated protein kinase 70 (ZAP-70) kinases, resulting in the phosphorylation of tyrosine residues located in the CD3 immunoreceptor tyrosine-based activation motifs (ITAMs) and the linker for activation of T cells (LAT) adaptor, respectively. (
  • During antigen and mitogen stimulation of lymphocytes, specific genetic programs are established by the coordinated activation of various signal transduction pathways, which in turn, lead to morphologic changes, cell division, differentiation, and the acquisition of immunological function. (
  • The temporal patterns of gene expression that underlie these processes in lymphocytes collectively span a time frame that extends from minutes to days, with the induction of immediate early and early response genes coinciding with that period of mitogenic stimulation required to commit a cell to a program of activation ( 1 ). (
  • One group of transcription factors essential for lymphocyte activation and immune function is the Rel/nuclear factor (NF)-κB proteins ( 2 ), homodimers and heterodimers composed of related subunits that are encoded by a small multigene family. (
  • As part of a strategy aimed at identifying genes regulated by Rel, the expression of genes normally induced early in lymphocyte activation were examined in c-rel −/− B and T cells. (
  • Our data suggest a defective activation of T regulatory cells in long-standing diabetics due to a lower expression of PD-1 on their surface. (
  • The present studies demonstrate that the IE genes of HCMV are transcribed in Jurkat cells (T lymphocytes) only after activation of the cells with mitogens. (
  • It is proposed that activation of lymphocytes results in expression of the IE genes of HCMV, in part via the activation of cellular trans-acting factors which interact with the 18- and 19-bp motifs in the HCMV IE promoter-regulatory region. (
  • Here we demonstrate the critical role of interleukin-17-producing marrow infiltrating lymphocytes (MILs) in OC activation and development of bone lesions in myeloma patients. (
  • Cytotoxic T lymphocyte antigen-4 (CTLA-4) is a regulatory molecule that suppresses T cell effector function following initial activation by costimulatory signals. (
  • This study shows that activation of IAP elements in normal normal mouse lymphocytes is highly selective. (
  • Rel is dispensable for normal embryonic development and hemopoiesis, but is essential for the division, survival, differentiation, and immune function of mature lymphocytes and macrophages ( 7 )( 8 )( 9 )( 10 )( 11 ). (
  • Neuroinflammation is a pathological hallmark of ALS in both transgenic rodent models and patients, and is characterized by proinflammatory T lymphocytes and activated macrophages/microglia. (
  • In the present study we have evaluated in parallel the level of TfR expression, ferritin, and IRE-BP in cultures of: (i) circulating human lymphocytes stimulated to proliferate by phytohemagglutinin (PHA) and (ii) circulating human monocytes maturing in vitro to macrophages. (
  • This is achieved by activating macrophages to destroy phagocytosed microbes via helper T-lymphocytes, or by directly killing infected cells via cytotoxic T-lymphocytes. (
  • Locally resident intraepithelial lymphocytes (IELs) are primarily T cells with potent cytolytic and immunoregulatory capacities, which they use to sustain epithelial integrity. (
  • Ferguson, A. Intraepithelial lymphocytes of the small intestine. (
  • Yoshikai, Y. The interaction of intestinal epithelial cells and intraepithelial lymphocytes in host defense. (
  • The adaptive T-regulatory cells are further subdivided into T-regulatory cells type 1 and T-helper cell type 3 that mediate suppression exclusively via the cytokines interleukin-10 and transforming growth factor-β, respectively. (
  • T regulatory Cell Suppression of CD8+ Lymphocyte Responses During FIV Infection. (
  • Furthermore, co-culture of CD8+ lymphocytes with CD4+CD25+ lymphocytes results in suppression of CD8+ IFNï § production during both the acute and chronic stages of infection. (
  • Regulatory B cells (Bregs or Breg cell) represent a small population of B cells which participates in immunomodulations and in suppression of immune responses. (
  • Another cytokine produced with an anti-inflammatory effect is TGF-β, which has a role in the suppression of T lymphocytes, for example in diabetes. (
  • 348, 203-213], the presence of CD3 + tumor-infiltrating lymphocytes (TILs) was found to correlate with improved survival in epithelial ovarian cancer. (
  • It is well known that tumor-infiltrating lymphocytes (TILs) and, to a lesser extent, peripheral blood lymphocytes from patients with advanced-stage cancer have a poor immune response. (
  • Tumor-infiltrating lymphocytes (TILs) are associated with pathological complete response (pCR) and survival after neoadjuvant chemotherapy (NAC) in patients with early breast cancer. (
  • The number of CD4+, CD25+, forkhead box p3+ (Foxp3+) lymphocytes was assessed via flow cytometry in ascites and peripheral blood from 24 women with epithelial ovarian cancer (EOC). (
  • The expression of CD3 + CD4 + T lymphocytes was detected by flow cytometry, and intestinal villi development was observed by intestinal paraffin section. (
  • The majority of T lymphocytes in atherosclerotic lesions are CD4 + T-helper cells with a phenotype characteristic of the proinflammatory T-helper 1 (Th1) subset. (
  • This study was aimed at characterizing phenotype and function of CD8 + CD28 − T regulatory cells infiltrating human cancer. (
  • During the acute stage of infection, plasma viremia as well as PBMC and LN lymphocyte phenotype was assessed at regular intervals. (
  • Regulatory T-cells, natural suppressor cells of the immune system, control pro-inflammatory T-cell responses, but can also contribute to disease by shifting to a pro-inflammatory T H 17-like phenotype. (
  • Our study demonstrates that Aspergillus fumigatus induces regulatory T-cells with a T H 17-like phenotype. (
  • We also demonstrate that these regulatory T-cells with a pro-inflammatory T H 17-like phenotype can be reprogrammed to their "classical" anti-inflammatory phenotype by activating Toll-like receptor 2 (TLR2), which regulates the induction of cytotoxic T-lymphocyte-associated protein 4 (CTLA4). (
  • Similarly, soluble CTLA4 could reverse the pro-inflammatory phenotype of Aspergillus- induced regulatory T-cells. (
  • In conclusion, our results suggest a role for regulatory T-cells with a pro-inflammatory T H 17-like phenotype in Aspergillus -associated immunopathology, and identifies key players, i.e. (
  • Given the chronicity and persistence of the parasite Trypanosoma cruzi in the Chagas disease victims, the homeostatic control of immune response to prevent tissue damage and limit the duration of the inflammatory process involves cells with regulatory potential as dendritic cells (DC) and regulatory T cells. (
  • The regulatory attributes of conventional human dendritic cells (DCs) in this respect merit further investigation. (
  • Background & Aims: Dendritic cells (DCs) initiate and sustain an efficient T-lymphocyte response. (
  • Mechanisms of Surveillance of Dendritic Cells by Regulatory T Lymphocytes. (
  • Limiting dilution analysis (LDA) of allogeneic and syngeneic murine mixed lymphocyte reactions was used to study the heterogeneity both of the responding spleen cells and of the stimulating antigen-presenting dendritic cells (DC). (
  • Determine the ability of treatment with short-term cultured autologous tumor-infiltrating lymphocytes (TIL) in combination with high-dose aldesleukin after a nonmyeloablative lymphocyte-depleting preparative regimen comprising cyclophosphamide and fludarabine phosphate to mediate tumor regression in patients with metastatic melanoma. (
  • Lymphocyte populations in human lymph nodes. (
  • This regulation is achieved by a number of cell populations acting through a set of shared regulatory pathways. (
  • Analysis of postvaccine peripheral blood lymphocytes (PBL) from patients showed an increased amount of interleukin (IL)-10 secretion on in vitro stimulation with IL-2 after successive vaccination. (
  • We therefore evaluated T regulatory cell frequencies and their PD-1 expression in the peripheral blood of long-standing diabetics under basal conditions and after CD3/CD28 stimulation. (
  • The promoter-regulatory region of the major immediate-early gene of human cytomegalovirus responds to T-lymphocyte stimulation and contains functional cyclic AMP-response elements. (
  • 6 , 7 Understanding these regulatory mechanisms in an autologous setting free of exogenous cytokines or allogeneic stimulation is especially important given that nearly all translational applications of DCs use autologous, and not allogeneic, cells. (
  • The anticipated mechanism of action is the stimulation of a cytotoxic T-lymphocyte (CTL) response against the cancer, which requires studying such cells within tumors. (
  • The main results are that both D 1 -like and D 2 -like DR are functionally active in human lymphocytes, although the D 1 -like DR stimulation results in stronger effects in comparison to the D 2 -like DR stimulation. (
  • Levels of lymphocyte- and monocyte-derived cytokines, such as IL-1, IL-2, IL-4, IL-6, and receptors (rec), such as soluble CD4 and IL-2R, are elevated in the circulation [ 54 ] ( Table 2 ). (
  • Despite numerous data concerning their immunophenotypes and secreted cytokines and chemokines, 1 the pathogenic roles of these Hodgkin lymphoma-infiltrating lymphocytes (HLILs) remain poorly understood. (
  • Resting B lymphocytes do not produce cytokines. (
  • Numerous immune regulatory functions have been reported for the IL-17 family of cytokines, presumably due to their induction of many immune signaling molecules. (
  • The understanding of these T-regulatory (T-reg) cells in the generation of antitumor cytolytic T lymphocyte (CTL) response is therefore important. (
  • 9 In multiple myeloma, we have previously shown that marrow infiltrating lymphocytes (MILs) are more effectively activated and expanded, possess greater antitumor activity than peripheral blood lymphocytes (PBLs) from the same patients, and thus represent more suitable T cells for adoptive immunotherapy in this disease. (
  • Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) functions as a negative regulator of endogenous and vaccine-induced antitumor immunity. (
  • In this context, a key role has emerged for cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) as a negative regulator of antitumor responses ( 5 ). (
  • Thus, a complex dynamic between effector and regulatory pathways underlies the antitumor effects of CTLA-4 blockade. (
  • The aim was to test our hypothesis that regulatory T cells dominate involved lymph nodes. (
  • In patients with metastatic cancer, those with a higher number of CD20 positive B lymphocytes in the lymph nodes are more likely to survive. (
  • In the first part, structure and function of the gene-regulatory network that controls differentiation of type I T-helper (Th1) cells is investigated. (
  • Many stimulatory combinations involve multivalent antigen and one or more antigen non-specific, non-MHC restricted T lymphocyte-derived growth and differentiation factors. (
  • Differentiation of T Lymphocytes. (
  • For this reason, the objective of this study is to evaluate the proportion of total DC, myeloid and plasmacytoid DC subpopulations and natural regulatory T cells in chronic chagasic patients and healthy control subjects. (
  • Analysis of the lympho-plasmacytic infiltrate in Crohn's disease with special reference to identification of lymphocyte subpopulations. (
  • Background: T lymphocytes and especially the subpopulations of CD8+ cells are believed to have a key role in COPD pathophysiology, but there are only few data regarding the role of these cells in COPD exacerbation. (
  • T-helper cell type (Th)2 lymphocytes play an important role in the initiation, progression and persistence of allergic diseases, including asthma. (
  • Regulatory T-cell response and tumor vaccine-induced cytotoxic T lymphocytes in human melanoma. (
  • The primary goal of the proposed clinical trial is to eliminate cancer tumor using an autologous cell therapy aiming at mounting an efficient immune anti-tumor response by selectively depleting regulatory T-cell during a controlled amount of time. (
  • This report shows that cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) plays a key role in T cell-mediated dominant immunologic self-tolerance. (
  • In the setting of donor lymphocyte infusion after hematopoietic stem cell transplantation, we postulated that T reg depletion could improve alloreactivity and likewise the graft-versus-tumor effect of donor T cells. (
  • The safety and efficacy of T reg -depleted donor lymphocyte infusion was studied in 17 adult patients with malignancy relapse after hematopoietic stem cell transplantation. (
  • It is noteworthy the effect of beta-mercaptoethanol is cell specific, i.e. the ratio of total versus spontaneous IRE-BP activity is different in activated lymphocytes and maturing monocytes. (
  • Murine and human T-lymphocyte GATA-3 factors mediate transcription through a cis-regulatory element within the human T-cell receptor delta gene enhancer. (
  • One of the members of this multigene family, cGATA-3, is most abundantly expressed in the T-lymphocyte cell lineage. (
  • These results support the hypothesis that increased numbers of regulatory T cells in the blood and tumours of colorectal cancer patients may influence the immune response against cancer and suggest that strategies to overcome regulatory T cell activity may be beneficial in the treatment of human colorectal cancer. (
  • A third type of lymphocyte, known as a natural killer or NK cell, comes from the same place as B and T cells. (
  • A comprehensive understanding of the complex, autologous cellular interactions and regulatory mechanisms that occur during normal dendritic cell (DC)-stimulated immune responses is critical to optimizing DC-based immunotherapy. (
  • Correspondingly, recent data in our laboratories indicate that periodontitis symptoms are accompanied by the absence of an important cell subset called regulatory T-cells. (
  • In the BW5147 T cell line, we have identified two independent regulatory pathways by which arachidonic acid (20:4) can alter gene expression. (
  • Collectively, the results identify the existence of multiple, independent, intracellular 20:4-mediated regulatory pathways operating simultaneously within this cell type. (
  • CD8+ T cell responses against Tat and Rev were found in up to 19 and 37% of HIV-1-infected individuals, respectively, indicating that these regulatory proteins are important targets for HIV-1-specific CTL. (
  • Upon engagement by B7-1 or B7-2, CTLA-4 expressed on the surface of activated T lymphocytes signals for cell-cycle arrest and attenuation of effector function ( 6 - 8 ). (
  • In recent years, major developments have been made in understanding various genetic and epigenetic regulatory processes that are critical for the generation of B cell repertoires. (
  • The approach was to assay CD4 + T-cell function in HL-infiltrating lymphocytes (HLILs) and paired peripheral blood mononuclear cells (PBMCs) of 24 patients. (
  • We found evidence for 3 mechanisms of action implicated in the suppressive functions of regulatory T cells: the inhibition of PBMCs by HLILs was ameliorated by neutralizing IL-10, by preventing cell-to-cell contact, and by blocking anti-cytotoxic T lymphocyte-associated antigen 4 (anti-CTLA-4). (
  • The Lymphocyte Biology Section (LBS) has made numerous contributions to the understanding of the cell biology of antigen processing and presentation by MHC class I and especially class II molecules. (
  • cAMP levels in lymphocytes and CD4+ regulatory T-cell functions are affected by dopamine receptor gene polymorphisms. (
  • Anti- CD5 (Lymphocyte antigen T1/Leu 1, p56 62, T cell surface glycoprotein CD5, T1) (MaxLight 750) by USBiological, Cat. (
  • Perturbations of regulatory mechanisms of TCR signaling and pathological implications, including new therapeutic approaches for immune based pathologies. (
  • We welcome authors to submit Original Research, Review and Case Reports focusing on the regulatory mechanisms of early intracellular signaling in T lymphocytes. (
  • Intestinal homeostasis arises from a highly dynamic balance between host protective immunity and regulatory mechanisms. (
  • however,at present,its role in ischemic brain injury remains controversial.The research on the mechanisms of regulatory T cells in ischemic stroke may contribute to further understanding of the pathogenesis of ischemic stroke and find new therapeutic targets. (
  • The ratio of regulatory to effector T cells was higher in patients than that in controls, suggesting that T regulatory cells were functional in patients. (
  • 12 These cells represent a newly defined lineage of T lymphocytes capable of producing interleukin-17 (IL-17) but not interferon-γ (IFN-γ) or IL-4. (
  • In the review, we will discuss the functional involvement of T cells in the pathogenesis of T2DM, especially the regulatory effects of T cells on chronic inflammation. (
  • Bregs have protective anti-inflammatory effects in the body and stop lymphocytes that cause inflammation . (
  • Regulatory lymphocytes and intestinal inflammation. (
  • Because breakdown in immune regulatory networks in the intestine leads to chronic inflammatory diseases of the gut, such as inflammatory bowel disease and celiac disease, regulatory lymphocytes are an attractive target for therapies of intestinal inflammation. (
  • Conclusion: The altered expression and regulatory capacity of co-IRs in SSc lymphocytes may contribute to disease pathophysiology by modulating the cytokine-mediated cross-talk of immune cells and fibroblasts at sites of inflammation and/or fibrosis. (
  • Sight-damaging ocular inflammation is often mediated by T-helper (Th) lymphocytes. (
  • To examine the pathogenicity of lymphocytes in immune-mediated ocular inflammation, we have developed an experimental system whereby lymphocytes sensitized against hen egg lysozyme (HEL) induce severe intraocular inflammation when adoptively transferred into recipients that transgenically express HEL in their eyes (denoted HEL-Tg mice). (
  • The regulatory effects of Bregs were described in various models of inflammation, autoimmune diseases, transplantation reactions and in anti-tumor immunity. (
  • Deeper molecular definitions of tumor-infiltrating-lymphocytes could thus offer therapeutic opportunities. (
  • To address this question we analysed the frequency and function of regulatory T cells in the peripheral blood and tumour infiltrating lymphocytes of colorectal cancer patients. (
  • The immune homeostasis associated with periodontal health requires a regulated immuno-inflammatory response, during which the presence of immune regulatory cells is essential to ensure a response that minimizes collateral tissue damage [3]. (
  • Rel/NF-κB proteins regulate gene expression by binding to specific decameric sequences (κB elements) located within the transcriptional regulatory regions of cellular genes, particularly those encoding proteins involved in immune, acute phase, and inflammatory responses ( 3 )( 4 ). (
  • Atherosclerosis is complex inflammatory disease of the arterial wall, in which T lymphocytes play a significant role. (
  • Our long-term objective is to address the physiological cause of periodontitis through an understanding of the inflammatory and regulatory processes of the periodontium. (
  • They usually compose only a minor proportion of the tumor, with the remainder mainly inflammatory lymphocytes. (
  • 1 Since the recognition that T lymphocytes are present in human atherosclerotic plaque nearly 2 decades ago, 2 research has focused on the functional importance of these cells in the atherosclerotic process. (
  • Functional cAMP response elements are present in the wild-type promoter-regulatory region and are associated with the 19-bp repeat sequences. (
  • We aimed to examine, in venous blood samples from healthy volunteers, the relationship between the arbitrary DR score and DR functional responses in human lymphocytes. (
  • Klein, J. R. Ontogeny of the Thy-1-, Lyt-2 + murine intestinal intraepithelial lymphocyte. (
  • Among various chemokine receptors, C-X-C motif chemokine receptor 4 (CXCR4) on CD4 T lymphocytes can be augmented by a synthetic glucocorticoid, dexamethasone ( 40 ). (
  • B lymphocytes with receptors specific for a particular hapten have been prepared through an antigen-affinity procedure. (
  • Here we show that mitogen-induced expression of interferon (IFN) regulatory factor 4 ( IRF-4 ), a lymphoid-specific member of the IFN family of transcription factors, is Rel dependent. (
  • Among those surveyed, IFN regulatory factor 4 ( IRF-4 ), a lymphoid-restricted member of the IFN family of transcription factors, emerged as a promising candidate. (
  • A gene on chromosome 6p25-p23 that encodes a member of the interferon regulatory transcription factor (IRF) family, which is characterised by an unique tryptophan pentad-repeat DNA-binding domain. (
  • Transcription of the IE genes is from an upstream enhancer promoter-regulatory region containing several different repeated sequence motifs. (
  • Ex-vivo depletion of CD4+CD25+ lymphocytes from lymph node suspensions significantly enhanced the production of IFNï § during the acute phase of infection. (
  • These proceedings highlight recent developments in lymphocyte development, Ig gene rearrangements and somatic hypermutation, chromatin structure modification, B lymphocyte signaling and fate, receptor editing, and autoimmunity. (
  • To our knowledge, this is the first study showing a correlation between DR gene variants and human T lymphocyte function. (
  • Immunoregulatory effects on T lymphocytes by human mesenchymal stromal cells isolated from bone marrow, amniotic fluid, and placenta. (
  • Mesenchymal stromal cells (MSCs) can generate immunological tolerance due to their regulatory activity in many immune cells. (
  • IRF-4 expression is rapidly induced in resting lymphocytes by mitogens ( 12 ) with kinetics that closely follow the nuclear induction of Rel ( 13 ). (
  • RIF is functionally active at concentrations of 1 X 10(-12) M or greater, rapidly binds to lymphocytes, and has a functionally effective half-life of approximately 1.5 h. (
  • Peripheral blood mononuclear cells (PBMC) from 18 chronic chagasic patients and 16 healthy control subjects were staining to myeloid DC Lin- HLA-DR+ CD11c+, plasmacytoid DC Lin-, HLA-DR+, CD123+ and natural regulatory T lymphocytes CD3+ CD4+ CD25+ Foxp3+ CD127low. (
  • On the contrary, it was found that the proportion of natural regulatory T cells was significantly higher in chronic chagasic patients than in healthy control subjects upon comparing the two. (
  • These results suggest that the higher proportion of natural regulatory T cells in chronic chagasic patients might contribute to the disease pathogenesis. (
  • During the chronic, asymptomatic phase of infection, IFNï § mRNA in CD8+ lymphocytes was assessed using real time RT-PCR following CD8+ co-culture with CD4+CD25+ lymphocytes. (
  • These results demonstrate the profound suppressive effect of CD4+CD25+ T regulatory cells on the CD8+ immune response during the acute and chronic stages of FIV infection. (
  • Eliminating CD8 + lymphocytes from monkeys during chronic SIV infection resulted in a rapid and marked increase in viremia that was again suppressed coincident with the reappearance of SIV-specific CD8 + T cells. (
  • Under basal conditions, the percentages of T regulatory cells were significantly higher while that of T effector cells were significantly lower in patients than in controls. (
  • Percentages of total PD-1 + , PD-1 low and PD-1 high expressing T regulatory cells did not change in patients and in controls. (
  • Two of the 17 patients developed graft-versus-host disease after their first T reg -depleted donor lymphocyte infusion and experienced a long-term remission of their malignancy. (
  • Four of the 15 patients who did not respond after a first T reg -depleted donor lymphocyte infusion received a second T reg -depleted donor lymphocyte infusion combined with lymphodepleting chemotherapy aimed to also eliminate recipient T reg s. (
  • These results suggest that T reg -depleted donor lymphocyte infusion is a safe, feasible approach that induces graft-versus-host or graft-versus-tumor effects in alloreactivity-resistant patients. (
  • In patients not responding to this approach, the combination of chemotherapy-induced lymphodepletion of the recipient synergizes with the effect of T reg -depleted donor lymphocyte infusion. (
  • Prior studies have demonstrated that a small proportion of blood lymphocytes from patients with human cytomegalovirus (HCMV) infection express only the viral immediate-early (IE) genes (L. Einhorn and A. Ost, J. Infect. (
  • Proportional change of CD4+CD25+ regulatory T cells after lymphocyte therapy in unexplained recurrent spontaneous abortion patients. (
  • Recent results have shown a correlation between survival and frequency of tumour infiltrating T lymphocytes in colorectal cancer patients. (
  • A higher density of tumour infiltrating regulatory T cells was found in patients with advanced as compared to early disease. (
  • PURPOSE: This phase II trial is studying how well laboratory-treated autologous lymphocytes and aldesleukin work when given after cyclophosphamide and fludarabine in treating patients with metastatic melanoma. (
  • Tumor-infiltrating lymphocyte (TIL) infusion and high-dose aldesleukin: Patients receive short-term cultured autologous TIL IV over 20-30 minutes on day 0. (
  • Methods: Peripheral blood mononuclear cells from healthy volunteers were used in a two-way mixed lymphocyte reaction. (
  • Representative images for the dual immunohistochemical and immunofluorescence detection of CD4 + FOXP + T-regulatory cells within human lung tissue. (
  • Lymphocytes infiltrating primitive tumor lesion and/or satellite lymph node from a series of 42 human cancers were phenotypically studied and functionally analyzed by suppressor assays. (
  • They account for approximately 1-3% of CD4+ T cells in human peripheral blood lymphocytes (PBLs) and about 5-10% of CD4+ T cells in the mouse spleen. (
  • Books 1 - 10 of about 45 related to Ontogeny of Human Lymphocyte Function . (
  • CD229/SLAMF3/Lymphocyte Antigen 9 Monoclonal antibody specifically detects CD229/SLAMF3/Lymphocyte Antigen 9 in Human, Mouse samples. (
  • However, the extent to which these proteins are targeted in natural HIV-1 infection as well as precise epitopes targeted by human cytotoxic T lymphocytes (CTL) remain to be defined. (
  • Recent studies, however, suggest adaptive immune system, especially T lymphocyte, also plays a pivotal role in the pathogenesis of T2DM. (
  • The immune system is a complex network of cells known as immune cells that include lymphocytes. (
  • Although cancers express tumor-associated Ags ( 1 , 2 ) and are infiltrated by tumor-specific T lymphocytes ( 3 , 4 ), they are able to evade immune surveillance. (
  • Results of these analyses showed that the presence of intratumoral lymphocytes and lymphocyte-predominant breast cancers were associated with a 31 and 41% pathological complete response (pCR) rates, respectively [ 2 ]. (
  • Regulatory T-lymphocytes mediate amyotrophic lateral sclerosis progression and survival. (
  • Erratum to Jenny S. Henkel, David R. Beers, Shixiang Wen, Andreana L. Rivera, Karen M. Toennis, Joan E. Appel, Weihua Zhao, Dan H. Moore, Suzanne Z. Powell and Stanley H. Appel (2013) Regulatory T‐lymphocytes mediate amyotrophic lateral sclerosis progression and survival. (
  • It is unknown, however, how glucocorticoid mobilizes lymphocytes in vivo. (
  • IRF4 is lymphocyte specific and negatively regulates Toll-like-receptor (TLR)-signalling, which is central to activating the innate and adaptive immune systems. (