Ethanol consumption is associated with impaired immunity. Our data demonstrate that even a single dose of a biologically relevant concentration (25-150 mM) of ethanol can down-regulate antigen-specific T lymphocyte proliferation. In contrast, ethanol augmented mitogen-induced T cell proliferation, suggesting that its inhibitory effect on antigen-specific T cell proliferation was due to its effects on monocytes (m phi s) rather than on T cells. The immunodepressive effects of ethanol on m phi antigen-presenting cell (APC) capacity were manifested whether alcohol treatment was limited to the antigen uptake-processing period only or was present during the entire period of antigen presentation. These inhibitory effects of ethanol were also evident on both the high-antigen-presenting, Fc gamma RI-negative (-31 +/- 17%), and low-antigen-presenting, Fc gamma RI-positive (-42 +/- 15%) m phi subpopulations. Further analysis demonstrated that ethanol inhibits the production of interleukin-1 beta (IL-1 beta) and
Human and rhesus macaque primary antigen‐specific T cells derived from infected or immunized individuals or animals are a valuable material with which to study cellular immune responses against pathogens and tumors
In this webinar, we feature Dr. Karen Anderson who utilized 3D Flow Analysis to deeply profile antigen specific T cells. Hear about the exciting biology uncovered from these rare cells utilizing this novel technique.
We found a selective increase in T-lymphocyte number in morbid obese subjects, which was mainly caused by an increase in CD4+ T-lymphocytes. Also, in morbid obese subjects TREC content was decreased in all T-lymphocyte subpopulations, demonstrating that the increase in T-lymphocytes is mainly caused by increased proliferation. Moreover, in morbid obese subjects we found increased plasma levels of IL-7 and CCL5, both potent enhancers of T-lymphocyte proliferation. Also, plasma of morbid obese subjects enhanced T-lymphocyte proliferation in vitro.. Finally, both CD4+ and CD8+ T-lymphocytes had some skewing of the TCR repertoire. ...
TY - JOUR. T1 - Cyclosporin A inhibits initiation but not progression of human T cell proliferation triggered by phorbol esters and calcium ionophores. AU - Kumagai, N.. AU - Benedict, S. H.. AU - Mills, G. B.. AU - Gelfand, E. W.. PY - 1988/12/1. Y1 - 1988/12/1. N2 - Cyclosporin A (CsA) is a potent inhibitor of T lymphocyte proliferation induced by Ag and mitogens. In an attempt to further delineate the mechanism of action of CsA, we have examined its effects on T cell proliferation induced by the combination of the phorbol ester, phorbol 12,13-dibutyrate (PDB), and the calcium ionophore, ionomycin. T cells were rendered competent as the result of a 30-min initial incubation with both drugs, after which the drugs were washed out. Competence is defined as the ability to subsequently proliferate in response to exogenously added IL-2 or PDB in the second phase of the culture, but not to synthesize IL-2 or proliferative without these additions. Addition of CsA (1 μg/ml) to the cells in the ...
Identification and characterization of antigen-specific T lymphocytes during the course of an immune response is tedious and indirect. To address this problem, the peptide-major histocompatability complex (MHC) ligand for a given population of T cells was multimerized to make soluble peptide-MHC tetramers. Tetramers of human lymphocyte antigen A2 that were complexed with two different human immunodeficiency virus (HIV)-derived peptides or with a peptide derived from influenza A matrix protein bound to peptide-specific cytotoxic T cells in vitro and to T cells from the blood of HIV-infected individuals. In general, tetramer binding correlated well with cytotoxicity assays. This approach should be useful in the analysis of T cells specific for infectious agents, tumors, and autoantigens. ...
Transmembrane signaling of normal human T cells was explored with mAbs directed at TCR, CD2, CD4, CD5, or CD8 antigens and highly purified CD4+ T cells and CD8+ T cells. Our experiments explicitly show that: (a) crosslinkage of TCR with the CD2 antigen, and not independent crosslinking of TCR and of CD2 antigen or crosslinking of either protein with the CD4 or CD8 antigen induces significant proliferation independent of co-stimulatory signals (e.g., accessory cells, recombinant lymphokines, or tumor promoter), (b) F(ab)2 fragments of mAb directed at the TCR and F(ab)2 anti-CD2, crosslinked with F(ab)2 fragments of rabbit anti-mouse IgG, promote the proliferation of highly purified T cells, (c) a prompt and sustained increase in intracellular free Ca2+ concentration results from crosslinkage of TCR with the CD2 antigen, (d) T cell proliferation induced by this novel approach is curtailed by EGTA and by direct or competitive inhibitors of PKC, (e) crosslinkage of TCR with the CD2 antigen ...
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Immunotherapy treatments for cancer are becoming increasingly successful, however to further improve our understanding of the T-cell recognition involved in effective responses and to encourage moves towards the development of personalised treatments for leukaemia immunotherapy, precise antigenic targets in individual patients have been identified. Cellular arrays using peptide-MHC (pMHC) tetramers allow the simultaneous detection of different antigen specific T-cell populations naturally circulating in patients and normal donors. We have developed the pMHC array to detect CD8+ T-cell populations in leukaemia patients that recognise epitopes within viral antigens (cytomegalovirus (CMV) and influenza (Flu)) and leukaemia antigens (including Per Arnt Sim domain 1 (PASD1), MelanA, Wilms Tumour (WT1) and tyrosinase). We show that the pMHC array is at least as sensitive as flow cytometry and has the potential to rapidly identify more than 40 specific T-cell populations in a small sample of T-cells ...
Lentiviral vectors have emerged as efficient tools for investigating T cell biology through their ability to efficiently deliver transgene expression into both dividing and nondividing cells. Such lentiviral vectors have the potential to infect a wide variety of cell types. However, despite this advantage, the ability to transduce primary human T cells remains challenging and methods to achieve efficient gene transfer are often time consuming and expensive. We describe a method for generating lentivirus that is simple to perform and does not require the purchase of non-standard equipment to transduce primary human T cells. Therefore, we provide an optimized protocol that is easy to implement and allow transduction with high efficiency and reproducibility.
Mature T lymphocytes of the CD8 or CD4 classes bear αβ T cell receptors (TCR) that are specific for a molecular complex consisting of a major histocompatibility complex class I or II (MHC class I or II) molecule bound to a unique self or foreign peptide
Polyfunctional CD4 or CD8 T cells are proposed to represent a correlate of immune control for persistent viruses as well as for vaccine mediated protection against infection. A well-suited methodology to study complex functional phenotypes of antiviral T cells is the combined staining of intracellular cytokines and phenotypic marker expression using polychromatic flow cytometry. In this study we analyzed the effect of an overnight resting period at 37°C on the quantity and functionality of HIV-1, EBV, CMV, HBV and HCV specific CD4 and CD8 T-cell responses in a cohort of 21 individuals. We quantified total antigen specific T cells by multimer staining and used 10-color intracellular cytokine staining (ICS) to determine IFNγ, TNFα, IL2 and MIP1β production. After an overnight resting significantly higher numbers of functionally active T cells were detectable by ICS for all tested antigen specificities, whereas the total number of antigen specific T cells determined by multimer staining remained
Mesenchymal stem cells (MSCs) suppress alloantigen-induced T-cell functions in vitro and infusion of third-party MSCs seems to be a promising therapy for graft-versus-host disease (GVHD).
The CD8 antigen is a disulfide-linked dimer, which exists either as a CD8α homodimer or as a CD8α/β heterodimer. CD8α is required for surface expression of CD8β. The molecular weight of each monomer of α or β is approximately 32-34 kDa. CD8 binds to a non-polymorphic domain (α3 domain) of MHC Class I molecules. CD8 is expressed on a subset of human peripheral blood T lymphocytes. A subset of NK cells possess the CD8 antigen but show low to medium density of expression. CD8α homodimer is expressed by NK cells and γ/δ+ T cells. CD8 is also present on most thymocytes where it is frequently co-expressed with CD4, and on a subpopulation of bone marrow cells. The CD8 molecule acts with the T Cell Receptor (TCR) as a coreceptor for MHC class I restricted antigen recognition. CD8 is widely used as a marker of cytotoxic T lymphocytes. *Alexa Fluor and Pacific Blue are registered trademarks of Molecular Probes, Inc ...
Effect of three kinds of anaesthetic drugs on postoperative recovery, regulatory T cells and T lymphoid cells in elderly patients
The CD2 antigen (LFA-2) is a monomeric 50 kDa glycoprotein. It was formerly described as the sheep red blood cell receptor, causing T-cell rosetting, and has been identified as the ligand for CD58 (LFA-3). It is also a receptor for CD48, CD59 and CD15, which binds to the multimeric form of CD2. CD2 is present on the majority of normal human peripheral blood T lymphocytes and a high percentage of NK cells. It is also expressed by all thymocytes ...
Experimental autoimmune encephalomyelitis (EAE) is an animal model for human multiple sclerosis (MS). The development of EAE relies on the generation of an auto...
Experimental autoimmune encephalomyelitis (EAE) is an animal model for human multiple sclerosis (MS). The development of EAE relies on the generation of an auto...
The data in this paper show that MD-1 is not associated directly with CD80/CD86, DEC205, or OX2 on the membrane of functional DC (Fig. 3⇑). However, inhibition of MD-1 synthesis achieved by incubating DC with the ODN-1 blocked MD-1 synthesis and then indirectly inhibited up-regulation of the costimulatory molecules CD80/CD86 in response to LPS (Fig. 2⇑). These ODN-1-altered DC-stimulated Th2-type cytokine production instead of Th1 cytokines when cultured with allogeneic responder splenocytes (Table I⇑), and proliferation and CTL generation was not seen. Instead, there was generation of cells that could suppress in a secondary test culture the allogeneic response of untreated C3H splenic T cells to unaltered allogeneic DC (Table II⇑). Generation of these suppressor cells was dependent on persistent OX2 expression on the ODN-1-treated DC, because anti-OX2 mAb blocked the effect. The ability of ODN-1-treated DC to enhance allograft survival in vivo via an OX2-dependent pathway (Fig. 4⇑) ...
T-cell chemiluminescence. A novel aspect of T-cell membrane activation studied with a Jurkat tumour cell line. Scand J Immunol. 1989 Aug; 30(2):265-9 ...
Un metodo per espandere γδ cellule T dalle cellule mononucleate del sangue periferico (PBMC) è descritta. PBMC cellule derivate γδ T...
Characterization of human leukocyte antigen (HLA) class I restricted epitopes derived from viral pathogens is imperative for formulating therapeutic interventions, as well as for vaccine design and monitoring. Sensitive, easy and cost-effective assays that measure the frequency of antigen-specific T lymphocytes are crucial for evaluating and improving vaccines and therapies. This paper reviews the ELISPOT technique that allows for quantifying HIV-specific T lymphocytes at the single cell level from peripheral blood by detection of antigen-induced cytokine secretion. The assay can be used successfully to quantify T cell immune responses in humans infected with different pathogens and to assess T cell immunogenicity of vaccines in phase I/II and III clinical trials. This review focuses on the ELISPOT methodology and discusses how it can be standardized and potentially used by multiple international laboratories attached to clinical trial sites.
Depasquale, jardieu P.; Fraker, P J.; and Luecke, R W., Regeneration of t-cell helper function in zinc deficient adult a/j mice. Abstr. (1978). Subject Strain Bibliography 1978. 1286 ...
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Interleukin 2 (IL-2, aldesleukin) was discovered as a T cell growth factor more than 30 years ago. IL-2 was the first human cytokine used therapeutically. IL-2 induces antigen specific T cells, and two important lymphocyte subsets: regulatory T cells (T-regs) and natural killer cells (NK) cells. T-regs have a critical role in self-tolerance and pathogenesis of autoimmune disease or graft versus host disease (GVHD), and they have been extensively studied in solid tumors, hematologic malignancies, viral hepatitis, and HIV infections. NK cells have a unique role in bridging innate and adaptive immunity. NK cells facilitate hematopoietic stem cell (HSC) engraftment reduce GVHD and increase graft-versus-leukemia (GVL) effects. NK cells have important roles on pathogenesis of malignancies, autoimmune disease and AIDS. Conventional dose IL-2 treatment promotes marked expansion of regulatory T cells, and NK cells but is associated with significant side effects. However, much lower doses of interleukin-2 ...
The relationship between T-cell metabolism and T cell effector function is little studied for human T cells. A recent publication by K. Renner et al. now reports about investigations of the group with human CD4 and CD8 T cells.. The authors used the CASY, to accurately and reliably determine the cell number and cell volume in proliferation assays and metabolic restriction experiments.. Read the publication here:. Metabolic plasticity of human T cells: Preserved cytokine production under glucose deprivation or mitochondrial restriction, but 2-deoxy-glucose affects effector functions. Kathrin Renner, Anna-Lena Geiselhöringer, Matthias Fante, Christina Bruss, Stephanie Dyer, Gabriele Saeed hammer, Katrin Peter, Katrin singer, Reinhard Andreesen, Petra Hoffmann, Peter Abubakar, Wolfgang Mr, Marina Kreutz.. Eur J Immunol. 2015 Sep;45(9):2504-16. two: 10.1002/eji.201545473. ...
Maloney began by explaining that CAR-T cells produced from distinct T-cell subsets differ in potency. NSG mice bearing Raji tumors (0.5x10 6tumor cell inoculation; day 0) were treated with human CAR-T cells manufactured from distinct T-cell subsets (on day 7). CAR-T cells produced from CD8 +T CMcells were highly potent ( Sommermeyer et al.2015).. Engineering selected T-cell subsets could enhance potency and allow delivery of the same cell product in all patients, potentially providing more uniform data on dose response and toxicity.. Pre-clinical studies have established that a defined composition of CD8 +T CMderived and CD4 +derived CAR T-cells provides optimal potency.. ...
It is suggested that human γδ T cells play significant roles during intracellular infections, such as tuberculosis (20), malaria (21), ehlrichosis (22), and many others (23, 24, 25, 26, 27, 28, 29, 30, 31). Evidence indicates that human T cells bearing Vγ2Vδ2-TCR, which constitute the vast majority of γδ T cells in healthy adults, respond to unique Ags in the extracts and/or supernatants of these bacteria and protozoa and are activated with respect to proliferation, cytokine production, and cytotoxic activity (17). These Ags include nonpeptide molecules such as a wide variety of small organic pyrophosphomonoesters (3, 4, 5, 7) and alkylamines (12) as well as unprocessed protein Ags (32, 33, 34). Although it has been indicated that the response takes place in a Vγ2Vδ2-TCR-dependent manner based on substantial evidence including the TCR gene transfer studies (15), knowledge of how human γδ T cells recognize such molecules has remained elusive.. It was indicated previously that activation ...
Providing CD8A (Cytotoxic & Suppressor T-Cell Marker); Clone C8/468 (Concentrate) - RA0041-C.1 ( Antibodies, Research Antibodies)
DI-fusion, le Dépôt institutionnel numérique de lULB, est loutil de référencementde la production scientifique de lULB.Linterface de recherche DI-fusion permet de consulter les publications des chercheurs de lULB et les thèses qui y ont été défendues.
Freshly isolated, human peripheral blood T (PBT) cells are largely resistant to the apoptotic effects of anti-CD3 monoclonal antibody, ionomycin, or phorbol 12-myristate 13-acetate (PMA). We demonstrate here, however, that PBT cells, including both CD4+ and CD8+ cell populations, can be readily induced to undergo apoptosis when cocultured with either autologous or allogeneic monocytes (Mo) in PMA-containing medium. Incubation of PBT cells with Mo at a ratio of 1:1 for 18 hr resulted in maximal levels (80%) of apoptotic cell death. The mechanism whereby Mo enable PBT cells to undergo apoptosis in PMA-containing medium appeared to depend on cell-cell contact or close proximity between Mo and PBT cells rather than solely via soluble mediators. It was demonstrated that Mo acquire the ability to prime PBT cells for apoptosis after treatment with PMA and that treated Mo maintain this ability even after fixation with formaldehyde. It was also found that once PBT cells became primed for apoptosis by ...
Recent clinical trials have demonstrated that a type of immune cell called T lymphocytes may play an important role in inducing the regression of different cancers, in particular of blood cancers. Other immune cells called macrophages accumulate in solid tumors and are numerous in growing tumors of poor prognosis. Based on these results, many people consider that, for cancer patients, lymphocytes are good guys and macrophages are bad guys. However, the reality is likely to be not that Manichean. Indeed, immune responses that are efficient against infection require efficient cooperations between different cell types. We have designed a local treatment for tumor-bearing mice which has been conceived on the model of an anti-infectious response, as if there was an infection at the level of the tumor. This resulted in a systematic tumor regression.. We perform an accurate kinetic analysis of the immune response by combining immunofluorescence in tumor sections with a global analysis of the ...
Melanie Chabaud has been awarded a Long-Term Postdoctoral Fellowship from the Human Frontier Science Program (HFSP) to investigate the molecular events leading to T cell arrest.. T cells constantly migrate through the peripheral lymphoid organs, briefly pausing to sample the antigenic peptides presented by antigen presenting cells. Long-lasting interactions with antigen presenting cells, resulting in sustained signalling, is required to generate a robust immune response. But what makes them stop and what happens when they do?. Melanie believes that increased membrane tension in T cells triggers the critical events leading to T cell arrest, including reorganisation of the cytoskeleton and initiation of signalling cascades. Using purpose-built microchambers, she can observe T cells under the microscope as they recognise their target antigen and stop. She can then observe the actin cytoskeleton remodelling and other changes at the molecular level.. After completing her Ph.D. at the Institut Curie ...
Tissue in monkeys infected with a close relative of HIV can ramp up production of a type of T cell that actually weakens the bodys attack against the invading virus. The discovery, in lymph nodes draining the intestinal tract, could help explain how the HIV virus evades the bodys immune defenses. [en español]
There are two different types of lymphocytes. B-lymphocytes (sometimes just called B-cells) produce antibodies. An antibody is a protein that can lock onto a distinctive part of a specific foreign organism. When this happens, the antibody signals to other immune cells to attack the organism.. T-lymphocytes (sometimes just called T-cells) are called different names depending on the molecules on their surface. CD4 cells (also known as CD4 T-lymphocytes, or T-helper cells) play a co-ordinating role in the immune system. They help B-lymphocytes identify foreign organisms (which they produce antibodies against). They also secrete substances that enable CD8 cells to reproduce. CD4 cells also activate macrophages (see below) to kill certain organisms, including many causes of AIDS-related illness. When CD4 cells are destroyed by HIV, all these parts of the immune system are disrupted. CD8 cells (also known as CD8 T-lymphocytes or cytotoxic T-cells) attach themselves to abnormal body cells, notably ...
HLA-A*02:01 PRAME142-151 Tetramer-SLYSFPEPEA-APC(Human Class I) from MBL.MHC tetramers can be used for direct detection of antigen specific T cells.
The clone 11A8, a mouse monoclonal antibody, recognizes a ~65 kDa cell surface glycoprotein known as CD226. It is a member of immunoglobulin superfamily containing two immunoglobulin-like variable domains. CD226 is widely expressed on peripheral blood T cells, NK cells, monocytes/macrophages, platelets and megakaryocytes and on a subset of B cells. It plays important role in the process of cytotoxic activities mediated by NK and T cells.
PositivelyPositive.ca is designed to create awareness around the many HIV and AIDS issues and promotes messages of positive living with HIV
T lymphocytes are cells of the immune system that produce factors regulating the function of other cells of immune system thereby shaping the systemic immune response. CD4+ T lymphocytes play a crucial role in directing the immune responses against foreign pathogens, damaged or transformed cells. However, when deregulated, the T cells may also mediate a number of autoimmune diseases such as type-1 diabetes, rheumatoid arthritis and multiple sclerosis. In addition, activated T cells mediate graft rejection and may significantly affect the development and progression of inflammatory diseases such as cardiovascular disease and stroke. Therefore, understanding the complex molecular mechanisms that regulate T cell effector functions may lead to development of therapeutic strategies designed to treat and/or alleviate T cell-mediated immune system disorders in humans. Our research focuses on unraveling the cellular and molecular mechanisms regulating T cell activation and communication with other cells ...
PI3Ks (phosphoinositide 3-kinases) regulate diverse cellular functions such as metabolism, growth, gene expression and migration. The p110delta isoform of PI3K is mainly expressed in cells of the immune system and contributes to cellular and humoral immunity. In the thymus, p110delta and p110gamma p …
Gene therapy. A researcher prepares culture dishes of gene-corrected T-lymphocytes. T-lymphocytes are white blood cells that play a crucial role in the immune system. This stock of lymphocytes is derived from cells taken from a patient with a suppressed immune system. The original sample was genetically altered to make the cells more active, and then cultured to produce large numbers. The cells can then be reintroduced into the patient to help restore the immune system. - Stock Image G210/0538
The day weve been warning you about for weeks is here, and its time to get your ducks in a row. Entries for the B&T Awards will close today at 5pm!. If you havent started your entry yet, were not mad, were just disappointed. But you can remedy that by getting your entry in before 5pm today.. In case you hadnt caught on yet, thats the on-time entry deadline. Today, Friday August 3, 5pm. Winning one of these awards is no easy feat - youll need a killer entry to win. Which means you definitely should have started already. Forget any other work you have to do today and get started right here.. The B&T Awards are Australias biggest, longest-running and most entertaining awards for the advertising, marketing and media industries, and are judged by a panel of industry experts.. And all you have to do to win is enter! Which you must do by the end of today.. To repeat, entries close today at 5pm - and the entry fee is $399 + GST.. Here at B&T, were super understanding when happy hour at the pub ...
Coloured scanning electron micrograph (SEM) of two T-lymphocyte white blood cells. Characteristic of T-lymphocytes are the long microvilli projecting from the cell surface. T-lymphocytes are susceptible to infection by the Human Immunodeficiency Virus (HIV), the causative agent of AIDS. Magnification 1300x at 35mm. - Stock Image C023/9649
CD3, PE-Cyanine5, clone: UCHT1, eBioscience™ 25 Tests; PE-Cyanine5 CD3, PE-Cyanine5, clone: UCHT1, eBioscience™ Primary Antibodies CD1 to CD5
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CD3 is an essential T cell co-receptorand defines T cell lineage. CD3is therefore an ideal T cell marker. This mini-review explains the structure of CD3, the genes involved in its expression, its function and the signal transduction pathways mediated by CD3 complex.
I was wondering if my transfections are not working because Im using the wrong cell line, I have been using HEK293, but is HEK293T better for transient and stable transfection? Also is there a difference with vendors (ie, some have better cell lines? lower passages perhaps?). Im just getting frustrated with these transfections that do not work. If anyone has any suggestions I would greatly appreciate it ...
Looking for the meaning of t-lymphocytes? Find out what is the meaning of t-lymphocytes on Phrases.net! The Webs largest and most authoritative phrases and idioms resource.
Looking for Major histocompatability complex? Find out information about Major histocompatability complex. In vertebrates, a family of genes that encode cell surface glycoproteins that regulate interactions among cells of the immune system, some components of the... Explanation of Major histocompatability complex
TY - JOUR. T1 - Primary human T lymphocytes engineered with a codon-optimized IL-15 gene resist cytokine withdrawal-induced apoptosis and persist long-term in the absence of exogenous cytokine. AU - Hsu, Cary. AU - Hughes, Marybeth S.. AU - Zheng, Zhili. AU - Bray, Regina B.. AU - Rosenberg, Steven A.. AU - Morgan, Richard A.. N1 - Copyright: Copyright 2017 Elsevier B.V., All rights reserved.. PY - 2005/12/1. Y1 - 2005/12/1. N2 - IL-15 is a common γ-chain cytokine that has been shown to be more active than IL-2 in several murine cancer immunotherapy models. Although T lymphocytes do not produce IL-15, murine lymphocytes carrying an IL-15 transgene demonstrated superior antitumor activity in the immunotherapy of B16 melanoma. Thus, we sought to investigate the biological impact of constitutive IL-15 expression by human lymphocytes. In this report we describe the generation of a retroviral vector encoding a codon-optimized IL-15 gene. Alternate codon usage significantly enhanced the translational ...
TY - JOUR. T1 - T-cell hyporesponsiveness induced by activated macrophages through nitric oxide production in mice infected with Mycobacterium tuberculosis. AU - Nabeshima, Shigeki. AU - Nomoto, Mari. AU - Matsuzaki, Goro. AU - Kishihara, Kenji. AU - Taniguchi, Hatsumi. AU - Yoshida, Shin Ichi. AU - Nomoto, Kikuo. PY - 1999. Y1 - 1999. N2 - In active tuberculosis, T-cell response to Mycobacterium tuberculosis is known to be reduced. In the course of Mycobacterium tuberculosis infection in mice, we observed that T-cell proliferation in response to M. tuberculosis purified protein derivative (PPD) reached the maximum level on day 7, then declined to the minimal level on day 14, and persisted at a low level through day 28 postinfection. The frequency of PPD-specific CD4 T cells in the spleen on day 28 decreased to one-sixth on day 7. To further investigate the mechanism of this T-cell hyporesponsiveness, we next analyzed the suppressive activity of spleen macrophages on T-cell function. The ...
TY - JOUR. T1 - The effect of dexamethasone, cyclosporine, and rapamycin on T-lymphocyte proliferation in vitro. T2 - Comparison of cells from patients with glucocorticoid-sensitive and glucocorticoid-resistant chronic asthma. AU - Haczku, Angela Franciska. AU - Alexander, Andrew. AU - Brown, Peter. AU - Assoufi, Basil. AU - Li, Baiqing. AU - Kay, A. Barry. AU - Corrigan, Christopher. PY - 1994. Y1 - 1994. N2 - Inhibition of T-lymphocyte activation may provide a useful approach to the treatment of chronic severe asthma. We compared rapamycin, a novel immunosuppressive drug, with cyclosporine and dexamethasone for its effects in inhibiting proliferation of T lymphocytes from patients with glucocorticoid-resistant and glucocorticoid-sensitive asthma. Phytohemagglutinin-stimulated peripheral blood T lymphocytes from 11 patients with clinically glucocorticoid-resistant and 8 patients with glucocorticoid-sensitive chronic asthma were tested for sensitivity to these drugs in a highly reproducible ...
The T cell receptor (TCR) V beta-determining region of two bacterial superantigens, staphylococcal enterotoxin A (SEA) and SEE, has been mapped to the COOH-terminal region of SEA and SEE using a panel of recombinant SEA/SEE hybrids. Total TCR V beta mRNA enrichment in human peripheral blood T cell cultures was determined by a novel single-tube amplification technique using a redundant V beta-specific primer. SEA routinely enriched mRNA coding for hV beta 1.1, 5.3, 6.3, 6.4, 6.9, 7.3, 7.4, and 9.1, while SEE, which is 83% homologous to SEA, enriched hV beta 5.1, 6.3, 6.4, 6.9, and 8.1 mRNA. Exchanging residues 206 and 207 was sufficient to convert in toto the TCR V beta response of human peripheral T lymphocytes. In addition, an SEA-reactive murine T cell line, SO3 (mV beta 17), unresponsive to wild-type SEE responded to SEE-S206N207, while an SEE-specific human T cell line, Jurkat (hV beta 8.1), unresponsive to SEA was stimulated strongly by SEA-P206D207. Exchanging all other regions of SEA and ...
We next examined the effect of thalidomide on cytokine production by the three T cell populations when stimulated by anti-CD3 in the absence of exogenous IL-2. Thalidomide induced a consistent concentration-dependent increase in IL-2 production at 12 h (time of peak production determined in preliminary kinetic experiments), in CD8+ and in bulk T cells (Fig. 3,A). Although a trend towards a thalidomide dose response in IL-2 production by purified CD4+ T cells was apparent, production of this cytokine was modest in comparison to that of bulk and CD8+ populations. Exposure to thalidomide consistently increased IFN-γ production by all three T cell populations. Since there was no clear peak in production of the latter cytokine, the results of a kinetic experiment are shown for CD4+ and CD8+ T cells (Fig. 3,B) using a single concentration of thalidomide (10 μg/ml). Again, the drug induced relatively greater production of IFN-γ by purified CD8+ T cells. However, the thalidomide-induced augmentation ...
Rubin, B; Hertel, wulff B.; and Kimura, A, Alloantigen-specific idiotype-bearing receptors on mouse t lymphocytes. I. Specificity characterization and genetic association with the heavy-chain igg allotype. (1979). Subject Strain Bibliography 1979. 4576 ...
TY - JOUR. T1 - Hydrogen Peroxide Triggers a Dual Signaling Axis To Selectively Suppress Activated Human T Lymphocyte Migration.. AU - Ball, Jennifer. AU - Vlisidou, Isabella. AU - Blunt, Matthew. AU - Wood, William. AU - Ward, Stephen. PY - 2017/5/1. Y1 - 2017/5/1. N2 - H2O2 is an early danger cue required for innate immune cell recruitment to wounds. To date, little is known about whether H2O2 is required for the migration of human adaptive immune cells to sites of inflammation. However, oxidative stress is known to impair T cell activity, induce actin stiffness, and inhibit cell polarization. In this study, we show that low oxidative concentrations of H2O2 also impede chemokinesis and chemotaxis of previously activated human T cells to CXCL11, but not CXCL10 or CXCL12. We show that this deficiency in migration is due to a reduction in inflammatory chemokine receptor CXCR3 surface expression and cellular activation of lipid phosphatase SHIP-1. We demonstrate that H2O2 acts through an Src ...
The migration of T lymphocytes is a vital component of the immune system, with roles in immunosurveillance and inflammation. The role of Phosphoinositide 3-kinase within T lymphocyte migration is unclear, with some evidence that it may be a disposable signal. Here, using Staphylococcal Enterotoxin B activated peripheral blood mononuclear cells and the T cell line CEM cells, the role of Phosphoinositide 3-kinase and its downstream kinases was investigated. CCL22 mediated CEM cell migration and CXCL12 mediated peripheral blood mononuclear cell migration were shown to be independent of Phosphoinositide 3-kinase using several different broad-spectrum Phosphoinositide 3-kinase inhibitors. However, these cells were Akt-dependent, as demonstrated by incubation with the Akt inhibitor Akti-1/2. Differences in the effect of the inhibitors on Akt activity were discovered, indicating that either Akt can be activated in the absence of Phosphoinositide 3-kinase, or differences exist regarding the relative ...
0065]Following incubation of the APCs with effector T lymphocytes obtained from a mammal immunized against the pathogen, the inventive method comprises screening for an immune response from the effector T lymphocytes. The immune response can be any suitable effector T lymphocyte immune response known in the art, including, but not limited to, cytokine secretion, effector T cell cytotoxicity, and immune activation of effector T cells. Preferably, the inventive method comprises screening for secretion by the effector T lymphocytes. In this regard, cytokine secretion from an effector T lymphocyte contacting an APC indicates that the effector T lymphocyte recognizes the antigen produced and displayed by the APC. Furthermore, it is well known in the art that effector T lymphocytes, such as effector helper T effector lymphocytes, secrete cytokines upon antigen recognition which promote different activities. In this regard, inflammatory or Th1 CD4 T cells produce interleukin-2 (IL-2), interferon gamma ...
Free Online Library: The Distribution of Activation Markers and Selectins on Peripheral T Lymphocytes in Preeclampsia.(Research Article, Report) by Mediators of Inflammation; Biological sciences B cells Analysis Disease susceptibility Physiological aspects Pregnant women T cells Health aspects Women Womens health
Description of disease T-suppressor cell. Treatment T-suppressor cell. Symptoms and causes T-suppressor cell Prophylaxis T-suppressor cell
Author Summary There is a desperate need for the development of new therapeutic strategies to eradicate HIV infection. HIV actively subverts the potent natural immune responses against it, particularly cellular cytotoxic T lymphocyte (CTL) responses. The development of a therapy that allows long-lived immune self-containment of HIV and restoration of these CTL responses by the host would be ideal. Through genetic manipulation of human blood-forming stem cells, we introduced a molecule- an HIV-targeting T cell receptor (TCR)-that allowed the generation of functional HIV-specific CTLs following differentiation within human tissues in a humanized mouse model. To assess if these newly developed, HIV-specific CTLs can allow active suppression of HIV replication, we infected these mice with HIV. We found that the development of genetically modified, HIV-specific CTLs in these mice results in the presence of a functional antiviral CTL response in vivo that significantly lowers viral replication following HIV
Utku N, Heinemann T, Tullius SG, Bulwin GC, Beinke S, Blumberg RS, Beato F, Randall J, Kojima R, Busconi L, Robertson ES, Schülein R, Volk HD, Milford EL, Gullans SR. Prevention of acute allograft rejection by antibody targeting of TIRC7, a novel T cell membrane protein. Immunity. 1998 Oct; 9(4):509-18 ...
Our study shows that (1) CD8+ T‐cell activation and memory generation occurs in response to atherogenic diet feeding in apoE−/− mice; (2) A small fraction of these activated CD8+ T cells in apoE−/− mice are antigen‐specific that are reactive to the p210 peptide fragment of apoB‐100, supporting the notion that p210 is a self‐antigen; and (3) Immunization of apoE−/− mice with the p210 peptide fragment altered the immune‐dominant epitopes, concurrent with reduced atherosclerosis. This has significant implications in our efforts to characterize immune functions in atherosclerosis and develop potential apoB‐100 peptide‐based vaccine candidates.4, 22. T‐cell activation is a hallmark feature of adaptive immunity. Naïve T cells undergo activation and clonal expansion of antigen‐specific T cells when encountering antigen presented by antigen‐presenting cells in the context of costimulatory signaling. Such antigen‐specific T cells further differentiate into effector and ...
CD27 is a lymphocyte-specific member of the TNF receptor family and has a TNF-related transmembrane ligand, CD70. The CD27/CD70 receptor-ligand pair cooperates with the TCR in the regulation of the peripheral T cell response. The study presented here reveals that CD27 may play a similar role in thymic pre-T cell development. We have previously cloned the cDNA encoding murine CD27, prepared specific mAbs and observed that murine CD27 is expressed on virtually all thymocytes, with the exception of a subpopulation of CD4-8- precursor T cells. It is shown here that induction of murine CD27 expression occurs at the transition from the CD4-8-25+ to the CD4-8-25- precursor T cell stage and is regulated by the pre-TCR. Therefore, we investigated whether CD27 contributes to pre-TCR-mediated thymocyte development. Pre-TCR function was mimicked by the induction of CD3 signaling in thymocytes of recombination activating gene (RAG)-deficient mice. This in vivo anti-CD3 epsilon mAb treatment induces an about ...
In cellular signal transduction, scaffold proteins provide binding sites to organize signaling proteins into supramolecular complexes and act as nodes in the signaling network. Furthermore, multivalent interactions between the scaffold and other signaling proteins contribute to the formation of protein microclusters. Such microclusters are prominent in early T cell signaling. Here, we explored the minimal structural requirement for a scaffold protein by coupling multiple copies of a proline-rich peptide corresponding to an interaction motif for the SH3 domain of the adaptor protein GADS to an N-(2-hydroxypropyl)methacrylamide polymer backbone. When added to GADS-containing cell lysates, these scaffolds (but not individual peptides) promoted the binding of GADS to peptide microarrays. This can be explained by the cross-linking of GADS into larger complexes. Furthermore, following import into Jurkat T cell leukemia cells, this synthetic scaffold enhanced the formation of microclusters of signaling ...
Heat shock protein (HSP, 60/65 kDa) is investigated as a candidate autoantigen in Behcets disease (BD), a systemic vasculitis of unknown origin, and a prominent response to disease-specific epitopes of mycobacterial and human HSP60/65 is described in BD patients. In this study, long-term T cell lines from peripheral blood of BD patients (n = 6) and controls (n = 7) were stimulated with mycobacterial recombinant HSP and purified protein derivate (PPD) and expanded with IL-2. In the BD group, 15 out 27 and in the controls, 25 out of 35 PPD specific T cell lines have responded to the synthetic peptides of the human HSP60. Out of the primarily HSP-specific T cell lines, 17/23 in patients and 8/8 in controls did recognize a peptide of human origin. T cell lines specifically reactive to 136-150, 179-197, 244-258 and 336-351 could be raised with similar frequency in both groups. In contrast to a previous report, T cells also reacted to peptide 425-441 frequently in both groups. The results ...
Adoptive T cell therapy to treat cancer in combination with re-directing specificity through T cell receptor (TCR) gene transfer, represents an effective therapeutic option. However, reduced effector responses due to the immunosuppressive tumour microenvironment and insufficient long-term engraftment of transferred cells represent two potential limitations. Tumours often employ mechanisms to inhibit T cell responses including secretion of TGFβ and depleting the tumour microenvironment of amino acids. The main aim of this PhD project was to develop a strategy to enhance T cell function for tumour therapy. The mammalian target of rapamycin (mTOR) pathway regulates CD8 T cell differentiation such that high mTOR activation leads to enhanced effector whilst low mTOR activation leads to increased T cell memory formation. Two retrovirus constructs have been designed whereby one expresses the positive mTOR regulator Rheb and the other expresses the negative mTOR regulator Pras40. Rheb transduction into ...
Interleukin 4 (IL-4) is secreted by activated T cells and pleiotropically modulates both B- and T-lymphocyte function. In murine helper (CD4+) T-cell clones IL-4 production appears to be regulated independently of interferon gamma and interleukin 2. To determine whether production of these lymphokines is also differentially regulated in uncloned human T cells, we studied lymphokine production by normal human peripheral T cells and T-cell subsets after in vitro polyclonal activation. After maximal induction of lymphokine expression, IL-4 mRNA was detectable in less than 5% of CD4+ and 1-2% of unfractionated T cells, whereas approximately 33% and 60% of CD4+ cells expressed detectable mRNA for interferon gamma and interleukin 2, respectively. This finding correlated with dramatically lower production of IL-4 mRNA and protein than of interferon gamma and interleukin 2 by peripheral blood and tonsillar T cells. The helper-inducer (CD4+ CD45R-) T-cell subset, which significantly enhances in vitro ...
BioAssay record AID 1270344 submitted by ChEMBL: Induction of cell proliferation in human Jurkat T cells at 200 uM after 24 hrs by tryphan blue assay.
In this report we show that it is possible to detect the expression of a G protein-coupled receptor, the A2AR, in human lymphocytes both on the basis of a functional assay (cAMP accumulation) and by flow cytometry using an antireceptor mAb. We were able to describe for the first time the distribution of A2AR among minor T cell subpopulations through the use of a combination of anti-A2AR mAb and mAbs that recognize T cell surface markers or cytokines. The principle findings of this study are that much higher levels of A2AR expression is found in T cells than in B cells (Fig. 3) and higher levels of cytokines are detected in activated T cells that express A2AR than in activated T cells that do not express these receptors (Figs. 6 and 7).. The detection of higher levels of cytokines among A2AR+ cells is surprising because A2AR-mediated signaling antagonizes the effects of T cell activation (Koshiba et al., 1997; Huang et al., 1997). Therefore, we expected that cytokine secretion would be the lowest ...
Background Different types of membrane microdomains (rafts) have been postulated to be present in the rear and front of polarized migrating T-lymphocytes. reorganization in human being T-lymphocytes and possible roles of flotillins in lymphocyte polarization. Results We studied flotillin reorganization and lateral mobility at the plasma membrane using immunofluorescence staining and FRAP (fluorescence recovery after photobleaching). We show that flotillins redistribute early upon chemokine stimulation and form very stable caps in the uropods of human peripheral blood T-lymphocytes colocalizing with the adhesion molecule PSGL-1 and activated ezrin/radixin/moesin (ERM) proteins. Chemokine-induced formation of stable flotillin caps requires Haloperidol (Haldol) integrity and dynamics of the actin cytoskeleton but is not abolished by inhibitors suppressing Rho-kinase or myosin II activity. Tagged flotillin-2 and flotillin-1 coexpressed in T-lymphocytes but Haloperidol (Haldol) not singly expressed ...
|span style=font-family:Times,serif;font-size:9pt;>The HIS51 monoclonal antibody specifically binds to the rat Thy-1 antigen (CD90) expressed by hematopoietic stem cells, early myeloid and erythroid cells, immature B lymphocytes in the bone marrow and peripheral lymphoid organs, thymocytes, recent thymic emigrants (a subset of CD45RC- peripheral T cells), neurons, glomerular mesangial cells, endothelium at inflammatory sites, mast cells, and bone marrow-derived dendritic cells. Rat dendritic epidermal T cells (DEC) are Thy-1-negative. CD90 is a GPI-anchored membrane glycoprotein of the Ig superfamily which is involved in signal transduction. In addition, there is evidence in the mouse that CD90 mediates adhesion of thymocytes to thymic stroma. HIS51 antibody cross-reacts with the mouse Thy-1.1 alloantigen of the AKR/J and PL strains, but not Thy-1.2 found on most strains. In the mouse, CD90 is found on thymocytes, most peripheral T lymphocytes, some intraepithelial T lymphocytes (IEL, DEC),
TY - JOUR. T1 - Epigenetics of human T cells during the G0→G1 transition. AU - Smith, Alexander E.. AU - Chronis, Constantinos. AU - Christodoulakis, Manolis. AU - Orr, Stephen J.. AU - Lea, Nicholas C.. AU - Twine, Natalie A.. AU - Bhinge, Akshay. AU - Mufti, Ghulam J.. AU - Thomas, N. Shaun B.. PY - 2009/8. Y1 - 2009/8. N2 - We investigated functional epigenetic changes that occur in primary human T lymphocytes during entry into the cell cycle and mapped these at the single-nucleosome level by ChIP-chip on tiling arrays for chromosomes 1 and 6. We show that nucleosome loss and flanking active histone marks define active transcriptional start sites (TSSs). Moreover, these signatures are already set at many inducible genes in quiescent cells prior to cell stimulation. In contrast, there is a dearth of the inactive histone mark H3K9me3 at the TSS, and under-representation of H3K9me2 and H3K9me3 defines the body of active genes. At the DNA level, cytosine methylation (meC) is enriched for ...
Tumor cell-derived exosomes (TEX) suppress functions of immune cells. Here, changes in the gene profiles of primary human T lymphocytes exposed in vitro to exosomes were evaluated. CD4(+) Tconv, CD8(+) T or CD4(+) CD39(+) Treg were isolated from normal donors peripheral blood and co-incubated with TEX or exosomes
The human T cell receptor for antigen (Ti) has recently been identified on IL-2 dependent T cell clones as a 90 kd disulfide-linked heterodimer comprised of one 49-51 kd alpha (alpha) and one 43 kd beta (beta) chain. These subunits are noncovalently associated with a monomorphic 20-25 kd T3 molecule. Here, we produce monoclonal antibodies to a human tumor (REX) derived from an earlier stage of thymic differentiation in order to determine whether clonotypic structures are expressed and to define the ontogeny of Ti. The results of SDS-PAGE and peptide map analyses indicate that an homologous T3-associated heterodimer is synthesized and expressed by REX. This glycoprotein shares several peptides in common with clonotypic structures on an IL-2 dependent T cell clone. In addition, similar Ti related molecules appear during intrathymic ontogeny in parallel with surface T3 expression. The latter findings provide the structural basis for the immunological competence observed exclusively within the T3+ thymocyte
The human T cell receptor for antigen (Ti) has recently been identified on IL-2 dependent T cell clones as a 90 kd disulfide-linked heterodimer comprised of one 49-51 kd alpha (alpha) and one 43 kd beta (beta) chain. These subunits are noncovalently associated with a monomorphic 20-25 kd T3 molecule. Here, we produce monoclonal antibodies to a human tumor (REX) derived from an earlier stage of thymic differentiation in order to determine whether clonotypic structures are expressed and to define the ontogeny of Ti. The results of SDS-PAGE and peptide map analyses indicate that an homologous T3-associated heterodimer is synthesized and expressed by REX. This glycoprotein shares several peptides in common with clonotypic structures on an IL-2 dependent T cell clone. In addition, similar Ti related molecules appear during intrathymic ontogeny in parallel with surface T3 expression. The latter findings provide the structural basis for the immunological competence observed exclusively within the T3+ thymocyte
Ertl, Hildegund; Gerike, Rainer und Koszinowski, Ulrich H. (1977): Virus-Specific T-Cell Sensitization. Requirements for vaccinia virus specific T cell sensitization in vivo. In: Journal of immunogenetics, Vol. 4: S. 515-522 ...
A membrane bound member of the TNF superfamily that is expressed on activated B-LYMPHOCYTES; MACROPHAGES; and DENDRITIC CELLS. The ligand is specific for the 4-1BB RECEPTOR and may play a role in inducing the proliferation of activated peripheral blood T-LYMPHOCYTES ...
BACKGROUND: Genome editing offers unique perspectives for optimizing the functional properties of T cells for adoptive cell transfer purposes. So far, PDCD1 editing has been successfully tested mainly in chimeric antigen receptor T (CAR-T) cells and human primary T cells. Nonetheless, for patients with solid tumors, the adoptive transfer of effector memory T cells specific for tumor antigens remains a relevant option, and the use of high avidity T cells deficient for programmed cell death-1 (PD-1) expression is susceptible to improve the therapeutic benefit of these treatments. METHODS: Here we used the transfection of CAS9/sgRNA ribonucleoproteic complexes to edit PDCD1 gene in human effector memory CD8+ T cells specific for the melanoma antigen Melan-A. We cloned edited T cell populations and validated PDCD1 editing through sequencing and cytometry in each T cell clone, together with T-cell receptor (TCR) chains sequencing. We also performed whole transcriptomic analyses on wild-type (WT) and
Video articles in JoVE about sequence alignment include Semi-automated Biopanning of Bacterial Display Libraries for Peptide Affinity Reagent Discovery and Analysis of Resulting Isolates, Creating and Applying a Reference to Facilitate the Discussion and Classification of Proteins in a Diverse Group, A Practical Guide to Phylogenetics for Nonexperts, Using Phylogenetic Analysis to Investigate Eukaryotic Gene Origin, Investigating Protein Sequence-structure-dynamics Relationships with Bio3D-web, Protein WISDOM: A Workbench for In silico De novo Design of BioMolecules, CAPRRESI: Chimera Assembly by Plasmid Recovery and Restriction Enzyme Site Insertion, Mapping Genome-wide Accessible Chromatin in Primary Human T Lymphocytes by ATAC-Seq, Isolation of Fidelity Variants of RNA Viruses and Characterization of Virus Mutation Frequency, Enhanced Reduced Representation Bisulfite Sequencing for Assessment of DNA Methylation at Base Pair Resolution, Optimization of Synthetic Proteins:
Therapies that Ag-specifically target pathologic T lymphocytes responsible for multiple sclerosis (MS) and other autoimmune diseases would be expected to have improved therapeutic indices compared with Ag-nonspecific therapies. We have developed a cellular immunotherapy that uses chimeric receptors to selectively redirect therapeutic T cells against myelin basic protein (MBP)-specific T lymphocytes implicated in MS. We generated two heterodimeric receptors that genetically link the human MBP84-102 epitope to HLA-DR2 and either incorporate or lack a TCRzeta signaling domain. The Ag-MHC domain serves as a bait, binding the TCR of MBP-specific target cells. The zeta signaling region stimulates the therapeutic cell after cognate T cell engagement. Both receptors were well expressed on primary T cells or T hybridomas using a tricistronic (alpha, beta, green fluorescent protein) retroviral expression system. MBP-DR2-zeta-, but not MBP-DR2, modified CTL were specifically stimulated by cognate MBP-specific T
At first glance, an association of a CD4 T cell-mediated disease with HLA class II gene products, whose function is to present peptides to CD4 T cells, appears easily explainable. Over the years, the most obvious, nonexclusive theories have been tested: instability and poor peptide binding of diabetogenic HLA class II molecules (6), unique peptide repertoire of the same molecules (7), T cells focused on the recognition of HLA-DQβ57 (8), failed thymic selection of autoreactive T cells (9), and abnormal T-cell binding to autoimmune peptide-MHC complexes (10). While all of those might bear truth and give some level of understanding of what the β57 residue might do, none could formally associate the mutation to a molecular mechanism leading to diabetes. The closest one to explaining the association of the same mutation with a disease was in the context of celiac disease, where the same HLA-DQ molecules are strongly predisposing to onset and also promote a frequent association with type 1 diabetes ...
TY - JOUR. T1 - Human amnion mesenchyme harbors cells with allogeneic T-cell suppression and stimulation capabilities. AU - Parolini, Ornella. AU - Magatti, Marta. AU - De Munari, Silvia. AU - Vertua, Elsa. AU - Gibelli, Lucia. AU - Wengler, Georg S.. PY - 2008. Y1 - 2008. N2 - Cells derived from the amniotic membrane of human placenta have been receiving particular attention because of their stem cell potentiality and immunomodulatory properties, which make them an attractive candidate source for cell therapy approaches. In this study, we isolated cells from the mesenchymal region of amnion and identified two subpopulations discordant for expression of the HLA-DR, CD45, CD14, and CD86 cellular markers. We therefore refer to the unfractionated cell population derived from this region as amniotic mesenchymal tissue cells (AMTC). We studied the suppressive and stimulatory characteristics of the unfractionated, HLA-DR-positive, and HLA-DR-negative AMTC populations and demonstrated that all three ...
The appearance of phosphatidylserine (PS) on the cell surface during apoptosis in thymocytes and cytotoxic T lymphocyte cell lines provokes PS-dependent recognition by activated macrophages. Flow cytometric analysis of transbilayer lipid movements in T lymphocytes undergoing apoptosis reveals that d …
T cells are an important part of the immune system. However, they are not only capable of destroying pathogens. They can also become harmful themselves. Researchers at the Technical University of Munich and the University Medical Center of the Johannes Gutenberg University Mainz have discovered the conditions under which certain T cells become the kind of pathogenic T cells associated with multiple sclerosis. Their results explain why certain treatments are not consistently effective.
Since TNFα is constitutively synthesized in the thymus, we explored its role during human early T-cell development. TNFα accelerated early T-cell differentiation and greatly increased the number of CD34-CD7+CD5- T-cell precursors generated in the in vitro DL-4 culture both for cord blood and adult CD34+ HSPCs. TNFα improved the production of CD34-CD7+CD5-/lo cells at the expense of myeloid and NK progenitors leading to a highly purified population of CD7+ T cell precursors. These T-cell precursors expressed early T-cell commitment markers as shown by extensive RNAseq analysis and had a high T-cell differentiation potential in vitro upon differentiation on OP9/DL1 cells and in vivo when transplanted to NOD/SCID/γc-/- mice. TNFα increased specifically the rate of proliferation in CD7+ T cell precursors between day 4 and 7 by promoting T-cell progenitors entry into the cell cycle through the activation of NFkB pathway. ...
The CD2 receptor on T lymphocytes is essential for T cell adhesion and stimulation by antigen presenting cells (APCs). Blockade of CD2 function is immunosuppressive in both model systems and humans, indicating the importance of CD2 for the cellular immune response. Although the affinity of the molecular interaction between CD2 and its counter-receptor, CD58, is relatively low when measured in solution, this interaction mediates tight adhesion within the 2D cell-cell interface. To understand the mechanisms responsible for regulating the avidity of the CD2-CD58 interaction, we measured the number, affinity, and lateral mobility of CD2 molecules on resting and activated T cells. Cell activation caused a 1.5-fold increase in the number of CD2 sites on the cell surface, and the 2D affinity of CD2 for CD58 increased by 2.5-fold. The combination of T cell activation and CD2 ligation to CD58 decreased the laterally mobile fraction of the ligated CD2. Together, these changes would substantially enhance CD2
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by Barbara Stranger, Ye CJ, Feng T, Kwon HK, Raj T, Wilson MT, Asinovski N, McCabe C, Lee MH, Frohlich I, Paik HI, Zaitlen N, Hacohen N, De Jager P, Mathis D, Regev A, Benoist C. T lymphocyte activation by antigen conditions adaptive immune responses and immunopathologies, but we know little about its variation in humans and its genetic or environmental roots. We analyzed gene expression in CD4(+) T cells during unbiased activation or in T helper 17 (T(H)17) conditions from 348 healthy participants representing European, Asian, and African ancestries. We observed interindividual variability, most marked for cytokine transcripts, with clear biases on the basis of ancestry, and following patterns more complex than simple T(H)1/2/17 partitions. We identified 39 genetic loci specifically associated in cis with activated gene expression. We further fine-mapped and validated a single-base variant that modulates YY1 binding and the activity of an enhancer element controlling the autoimmune-associated ...
A central question in T cell development is what makes cortical thymocytes respond to stimulation in a qualitatively different way than any other thymocyte subset. Part of the answer is that AP-1 function changes drastically at two stages of T cell development. It undergoes striking down-regulation as thymocytes differentiate from immature, CD4^-CD8^- double-negative (DN) TCR^- thymocytes to CD4^+CD8^+ double-positive (DP) TCR^(lo) cortical cells, and then returns in the cells that mature to TCR^(high), CD4^+CD8^- or CD4^-CD8^+ single-positive (SP) thymocytes. At all three stages, the jun family mRNAs can be induced similarly. However, we demonstrate that DP cortical thymocytes are specifically impaired in c-fos and fosB mRNA induction, even when stimuli are used that optimize survival of the cells and a form of in vitro maturation. fra-2 expression is induction independent but much lower in DP cells than in the other subsets. Overall Fos family protein induction accordingly is severely ...
1. T-cell proliferation is critical for mounting an effective adaptive immune response. It is regulated by signals through the T-cell receptor, through co-stimulation and through cytokines such as interleukin-2 (IL-2). Phosphatidylinositol 3-kinase (PI3K) lies downstream of each of these pathways and has been directly implicated in the regulation of lymphocyte proliferation. 2. In this study, we have shown that PI3K regulates cyclin D2 and cyclin D3, the first cell cycle proteins induced in T-cell proliferation, transcriptionally and post-transcriptionally. In T-lymphoblasts, LY294002, a PI3K inhibitor, prevents the induction of both D-type cyclin mRNA and protein, while rapamycin inhibits the induction of protein. Rapamycin inhibits mammalian target of rapamycin (mTOR), which lies downstream of PI3K. 3. Furthermore, our data show that the combination of LY294002 and rapamycin results in a co-operative inhibition of T-cell proliferation. This co-operation occurs in Kit225 cells stimulated with ...
TY - JOUR. T1 - Antigen-stimulated apoptotic T-cell death in HIV infection is selective for CD4+ T cells, modulated by cytokines and effected by lymphotoxin. AU - Clerici, Mario. AU - Sarin, Apurva. AU - Berzofsky, Jay A.. AU - Landay, Alan L.. AU - Kessler, Harold A.. AU - Hashemi, Farah. AU - Hendrix, Craig W.. AU - Blatt, Stephen P.. AU - Rusnak, Janice. AU - Dolan, Matthew J.. AU - Coffman, Robert L.. AU - Henkart, Pierre A.. AU - Shearer, Gene M.. PY - 1996. Y1 - 1996. N2 - Objective: To characterize the mechanism of in vitro antigen-induced apoptotic T-cell death in the peripheral blood mononuclear cells (PBMC) of HIV-1-infected individuals. Design and methods: PBMC from HIV-1-infected and uninfected individuals were unstimulated or stimulated with HIV-1 envelope synthetic peptides (Env) or influenza A virus to determine the extent of antigen-stimulated apoptotic T-cell death, whether this death was limited to the CD4+ subset, and the effects of cytokines on T-cell death. Death was ...