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
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. ...
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 ...
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 ...
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 ...
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.
This project aims at studying the interaction between the affected tissues in SSc and the autoreactive immune cells. The focus lies on regulatory T (Treg) cells that are crucial in keeping autoreactive immune cells under control.. We assume that Treg cells are functionally or quantitatively decreased in SSc. Therefore in vitro culturing of Treg cells and infusion into patients and/or in vivo expansion of Treg cells using selective interleukin-2 (IL-2)-antibody complexes might improve disease. This therapy might be applicable also to other rare diseases where a weakening of Treg cells is suspected, including primary immunodeficiency syndromes with immune dysregulation. Additionally it might be useful for treatment after hematopoietic stem cell transplantation, including patients suffering from rare diseases, where chronic graft-versus-host disease develops.. In order to test these hypotheses, we will perform T reg gain and loss of function experiments in three mice models of SSc, and the impact ...
Toxoplasmosis is an important cause of congenital disease, and it is one of the most common opportunistic infections in patients with acquired immunodeficiency syndrome. The need for a reliable experimental model of this infection is crucial not only for achieving a better understanding of the patho-physiology of the disease, but also for developing better methods for evaluating new therapeutic regimens. The purpose of the present study was to investigate the role of CD4+CD25+ T regulatory lymphocytes in mice infected with Toxoplasma gondii. T regulatory (Treg) cells have been shown to play an important role in our immune system in controlling the activity of other T lymphocytes. These cells are differentiated from other T lymphocyte populations based on the co-expression of CD4 and CD25 and expression of the Foxp3 gene. The results of several recent studies have suggested that certain pathogens may be able to increase their survival in the host by exploiting T reg cell activity. T regulatory cells have
PubMedID: 26615095 | Mechanisms of Surveillance of Dendritic Cells by Regulatory T Lymphocytes. | Progress in molecular biology and translational science | 11/29/2015
CD4+CD25+ regulatory T cells (Treg) play a critical role to maintain self-tolerance and the control of autoimmunity. These cells are characterized by expression of the transcription factor FOXP3 and possess potent immunosuppressive activity. Recent results by our lab and by others have shown that several subpopulations of Treg exist in humans. However, phenotypic, functional and molecular properties of these Treg subpopulations have remained poorly defined. The goal of the project was to investigate the heterogeneity of the human Treg cell compartment in order to better understand the role of these cells in controlling immune responses in health and disease. We have described three different subsets of Treg cells in adult peripheral blood: CD25hi FOXP3hi CD45RA- HLADR+ (aTreg), CD25hi FOXP3intm CD45RA- HLADR- (cTreg) and CD25hi FOXP3intm CD45RA+ HLADR- (nTreg). To assess the molecular characteristics of these three different subsets and to reliably define them, we have established their gene ...
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In animal studies, CHOP researchers advance new approach to anti-tumor immunotherapy. By carefully adjusting the function of crucial immune cells, scientists may have developed a completely new type of cancer immunotherapy-harnessing the bodys immune system to attack tumors. To accomplish this, they had to thread a needle in immune function, shrinking tumors without triggering unwanted autoimmune responses.. The new research, performed in animals, is not ready for clinical use in humans. However, the approach, making use of a key protein to control immune function, lends itself to further study using candidate drugs that employ the same mechanisms.. "This preclinical study demonstrates proof of principle that using a drug to regulate the function of a special, immunosuppressive subset of so-called T-regulatory (Treg) cells safely controls tumor growth," said study leader Wayne W. Hancock, M.D., Ph.D., of the Division of Transplant Immunology at The Childrens Hospital of Philadelphia (CHOP). ...
TY - JOUR. T1 - MTOR coordinates transcriptional programs and mitochondrial metabolism of activated Treg subsets to protect tissue homeostasis. AU - Chapman, Nicole M.. AU - Zeng, Hu. AU - Nguyen, Thanh Long M.. AU - Wang, Yanyan. AU - Vogel, Peter. AU - Dhungana, Yogesh. AU - Liu, Xiaojing. AU - Neale, Geoffrey. AU - Locasale, Jason W.. AU - Chi, Hongbo. PY - 2018/12/1. Y1 - 2018/12/1. N2 - Regulatory T (Treg) cells derived from the thymus (tTreg) and periphery (pTreg) have central and distinct functions in immunosuppression, but mechanisms for the generation and activation of Treg subsets in vivo are unclear. Here, we show that mechanistic target of rapamycin (mTOR) unexpectedly supports the homeostasis and functional activation of tTreg and pTreg cells. mTOR signaling is crucial for programming activated Treg-cell function to protect immune tolerance and tissue homeostasis. Treg-specific deletion of mTOR drives spontaneous effector T-cell activation and inflammation in barrier tissues and is ...
Clone REA664 recognizes the mouse CD44 antigen, which is also known as Pgp-1, HCELL, HUTCH-I, HCAM, HERMES, or Ly-24. CD44 is a 80-95 kDa membrane glycoprotein and expressed by a variety of hematopoetic and non-hematopoetic cells. Different isoforms are generated by alternative splicing. Clone REA664 reacts with all isoforms and both allelic forms of CD44. CD44 functions as a receptor for hyaluronic acid (HA) and mediates cell-cell and cell-matrix interactions through its affinity for HA, and possibly also through its affinity for other ligands, such as osteopontin, collagens, and matrix metalloproteinases (MMPs). The interaction between galectin-9 and CD44 increases the stability and function of adaptive regulatory T cells. CD44 expression is upregulated on naive T cells upon activation and high CD44 expression is maintained on memory T cells. Therefore, CD44 is often used to discriminate CD44high antigen-experienced T cells from CD44low (CD62L+ ) naive T cells. Additional information: Clone REA664
Our research focuses on the function of different types of human memory and regulatory T cells. CD4+ memory and regulatory T cells are highly heterogeneous populations that can be sub-divided into various subsets with different functions. In particular, memory T cells secrete different types of effector cytokines and can be classified into IFN- secreting Th 1 cells, which activate phagocytes to eliminate intracellular bacteria and viruses, IL-4 secreting Th 2 cells that promote IgE production and eosinophil activation to fight parasitic worms, and IL-17 producing Th 17 cells that induce the recruitment of neutrophils to kill extracellular bacteria and fungi. Conversely, regulatory T cells (Tregs) suppress immune responses and inhibit autoimmunity in mouse models, and possess therefore therapeutic potential in autoimmune diseases. They can be subdivided into natural Tregs, which become committed to the Treg lineage already upon thymic maturation, and into adaptive ones, which acquire ...
Description of disease T-suppressor count. Treatment T-suppressor count. Symptoms and causes T-suppressor count Prophylaxis T-suppressor count
By carefully adjusting the function of crucial immune cells called Tregs, scientists may have developed a completely new type of cancer immunotherapy-harnessing the bodys immune system to attack tumors.
This article is from PLoS ONE, volume 9.AbstractCD4+CD25+Foxp3+ regulatory T cells (Tregs) can inhibit cytotoxic responses. Though several studies have...
FOXP3(+)CD25(+)CD4(+) regulatory T (Treg) cells, crucial for the maintenance of immunological self-tolerance, are abundant in tumors. Most of them are chemo-attracted to tumor tissues, expanding locally and differentiating into a Treg-cell subpopulation that strongly suppresses the activation and ex …