Article

Mechanism of T regulatory cell function

Frankel Laboratory, Center for Stem Cell Research, Department of Pediatric Hematology-Oncology, Schneider Children's Medical Center of Israel, Petach Tikva, Israel.
Autoimmunity Reviews (Impact Factor: 7.93). 06/2008; 7(5):370-5. DOI: 10.1016/j.autrev.2008.03.001
Source: PubMed

ABSTRACT

Regulatory T cells (Treg) play a pivotal role in tolerance to self-antigens and tissue grafts, and suppression of autoimmune reactions. These cells modulate the intensity and quality of immune reactions through attenuation of the cytolytic activities of reactive immune cells. Treg cells operate primarily at the site of inflammation where they modulate the immune reaction through three major mechanisms: a) direct killing of cytotoxic cells through cell-to-cell contact, b) inhibition of cytokine production by cytotoxic cells, in particular interleukin-2, c) direct secretion of immunomodulatory cytokines, in particular TGF-beta and interleukin-10. In addition to differential contributions of these mechanisms under variable inflammatory conditions, mechanistic complexity and diversity evolves from the diverse tasks performed by various Treg cell subsets in different stages of the immune reaction. Here we attempt to integrate the current experimental evidence to delineate the major suppressive pathways of Treg cells.

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Available from: Nadir Askenasy
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    • "The differentiation of Th17 cells have been shown to depend on another CD4+ subset, the regulatory T cells (Treg). CD4+ Foxp3+ regulatory T cells suppress effector T cells in various pathological conditions, including inflammation, autoimmunity, cancer, and organ transplantation (Askenasy et al., 2008). They are especially important in maintaining self-tolerance and inhibiting the development of autoimmunity (Wang et al., 2007; Sakaguchi, 2005). "

    Full-text · Dataset · Jul 2014
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    • "The differentiation of Th17 cells have been shown to depend on another CD4+ subset, the regulatory T cells (Treg). CD4+ Foxp3+ regulatory T cells suppress effector T cells in various pathological conditions, including inflammation, autoimmunity, cancer, and organ transplantation (Askenasy et al., 2008). They are especially important in maintaining self-tolerance and inhibiting the development of autoimmunity (Wang et al., 2007; Sakaguchi, 2005). "

    Full-text · Dataset · Feb 2014
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    • "Like CD4+CD25+FOXP3+ Tregs, the suppressive activity of CD4+LAP+ Tregs has been shown to be dependent on both TGF-β1 and IL-10 in vitro [14], [34]. We found that serum TGF-β1 levels were reduced in ACS patients compared with those of CSA and CPS patients, but we failed to detect a significant difference in IL-10 levels. "
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    ABSTRACT: CD4(+) latency-associated peptide (LAP)(+) regulatory T cells (Tregs) are a newly discovered T cell subset in humans and the role of these cells in patients with acute coronary syndrome (ACS) has not been explored. We designed to investigate whether circulating frequency and function of CD4(+)LAP(+) Tregs are defective in ACS. One hundred eleven ACS patients (acute myocardial infarction and unstable angina) and 117 control patients were enrolled in the study. The control patients consisted of chronic stable angina (CSA) and chest pain syndrome (CPS). The frequencies of circulating CD4(+)LAP(+) Tregs and the expression of the transmembrane protein glycoprotein-A repetitions predominant (GARP) on CD4(+) T cells were determined by flow cytometry. The function of CD4(+)LAP(+) Tregs was detected using thymidine uptake. Serum interleukin-10 (IL-10) and transforming growth factor-β protein (TGF-β) levels were detected using ELISA and expression of GARP mRNA in peripheral blood mononuclear cells (PBMCs) was measured by real time-polymerase chain reaction. We found ACS patients had a significantly lower frequency of circulating CD4(+)LAP(+) Tregs, and the function of these cells was reduced compared to controls. The expression of GARP in CD4(+) T cells and the serum levels of TGF-β in ACS patients were lower than those of control patients. The serum levels of IL-10 were similar between the two cohorts. A novel regulatory T cell subset, defined as CD4(+)LAP(+) T cells is defective in ACS patients.
    Full-text · Article · Feb 2014 · PLoS ONE
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