The role of regulatory T cells in antigen-induced arthritis: aggravation of arthritis after depletion and amelioration after transfer of CD4+ CD25+ T cells (original) (raw)
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CD4 + CD25 + regulatory T cells in autoimmune arthritis
Immunological Reviews, 2010
CD4 + CD25 + regulatory T (Treg) cells can play a critical role in the prevention of autoimmunity, as evidenced by the cataclysmic autoimmune disease that develops in mice and humans lacking the key transcription factor forkhead box protein 3 (Foxp3). At present, however, how and whether Treg cells participate in the development of rheumatoid arthritis (RA), which has both systemic manifestations and a joint-targeted pathology that characterizes the disease, remains unclear. In this review, we describe work that has been carried out aimed at determining the role of Treg cells in disease development in RA patients and in mouse models of inflammatory arthritis. We also describe studies in a new model of spontaneous autoimmune arthritis (TS1×HACII mice), in which disease is caused by CD4 + T cells recognizing a neo-self-antigen expressed by systemically distributed antigen-presenting cells. We show that TS1×HACII mice develop arthritis despite the presence of CD4 + CD25 + Foxp3 + Treg cells that recognize this target autoantigen, and we outline steps in the development of arthritis at which Treg cells might potentially act, or fail to act, in the development of inflammatory arthritis.
Regulatory T cells in rheumatoid arthritis
Arthritis Res …, 2005
Apart from the deletion of autoreactive T cells in the thymus, various methods exist in the peripheral immune system to control specific human immune responses to self-antigens. One of these mechanisms involves regulatory T cells, of which CD4+CD25+ Tcells are a major subset. Recent ...
Role of regulatory T cells in rheumatoid arthritis: facts and hypothesis
Autoimmunity Highlights, 2010
Regulatory T cells (Treg) are a CD4 + lymphocyte subset involved in self-tolerance and autoimmunity prevention. There is evidence for a phenotypic and/or functional impairment of this cell subset during the natural history of several chronic autoimmune/inflammatory diseases, including rheumatoid arthritis (RA). Although the intracellular transcription factor FoxP3 is thought to be the master regulator of Treg cell function, a number of other molecules expressed on the cell surface have been proposed for the identification of Treg cells. This is important in order to favour their possible selective isolation and in the development of new therapeutic strategies. In the present paper, available data on phenotypic and functional characterization of Treg cells in both peripheral blood and synovial fluid from RA patients are reviewed and their possible pathogenic role in triggering and perpetuating rheumatoid joint inflammation is discussed.
Journal of immunology (Baltimore, Md. : 1950), 2016
Promising immunotherapeutic strategies are emerging to restore tolerance in autoimmune diseases by triggering an increase in the number and/or the function of endogenous regulatory T (Treg) cells, which actively control pathological immune responses. Evidence suggests a remarkable heterogeneity in peripheral Treg cells that warrants their better characterization in terms of phenotype and suppressive function, to determine which subset may be optimally suitable for a given clinical situation. We found that repetitive injections of immature dendritic cells expanded Foxp3-negative CD49b(+) Treg cells that displayed an effector memory phenotype. These expanded Treg cells were isolated ex vivo for transcriptome analysis and found to contain multiple transcripts of the canonical Treg signature shared mainly by CD25(+) but also by other subphenotypes. We characterized the CD49b(+) Treg cell phenotype, underscoring its similarities with the CD25(+) Treg cell phenotype and highlighting some ...
Activated T cells complicate the identification of regulatory T cells in rheumatoid arthritis
Cellular Immunology, 2008
Most cell surface markers for CD4 + CD25 + regulatory T cells (Tregs) are also expressed by activated nonregulatory T cells. Recently, CD127 down-regulation was found to identify functional Tregs in healthy individuals, but there are no data from patients with inflammatory conditions. We examined peripheral blood mononuclear cells (PBMC) from rheumatoid arthritis patients with active inflammation and from healthy controls, and found that CD4 + T cells contained an equal proportion of CD25 + CD127 À /low cells in both groups. In patients, not all these cells expressed intracellular FOXP3. Upon activation by anti-CD3/ anti-CD28, PBMC rapidly down-regulated CD127, while FOXP3 up-regulation was transitory and occurred in fewer cells. The activated cells were not anergic to restimulation and had no suppressive effects. The distinct kinetics indicate that the FOXP3 À CD127 À /low cells in rheumatoid arthritis patients most likely represent activated non-regulatory T cells. This complicates the use of CD127 for identification of Tregs in inflammatory diseases.
Levels of Regulatory and Effector T Cells in Patients with Rheumatoid Arthritis
2009
CD4+CD25+ regulatory T cells and CD4+CD25- effector T cells are crucial in maintaining immune system homeostasis and are thus potential therapeutic targets for autoimmune disease, such as rheumatoid arthritis (RA). Forkhead box p3 (Foxp3), which is required for regulatory T (Treg) cell development and its suppressive function, is also critical in sustaining normal immune function. In the present study, the