Characterization of regulatory T cells in humans
- Fanny Monneaux1
© Biomed Central Ltd 2001
Received: 25 July 2001
Accepted: 25 July 2001
Published: 25 July 2001
Regulatory T cells with the ability to prevent or regulate autoimmune disease have been demonstrated in several different experimental systems (see Additional information ). Studies have shown that this potent CD4+ immunoregulatory T-cell population can be defined by expression of the interleukin (IL)-2 receptor a chain (CD25). CD4+ CD25+ T cells are anergic to stimulation via T-cell receptors and suppress proliferation of CD4+CD25- lymphocytes in vitro. This suppression was shown to be cytokine-independent but required cell-cell contact to be efficient. This study was undertaken to establish the existence of such T-cell populations in humans.
CD4+CD25+ T cells were purified from human thymus lymphocytes and peripheral blood lymphocytes (PBLs). As has been shown in mice, these cells proliferated poorly in response to mitogenic stimulation, and this defect was reversed by exogenous IL-2. CD4+CD25+ T cells expressed cytotoxic T lymphocyte associated antigen (CTLA)-4 and CD122 molecules, and suppressed proliferation of CD4+CD25- T cells in a dose-dependent manner. This suppression required direct interactions between CD4+CD25+ and CD4+CD25- T cells in vitro. Unstimulated thymic CD4+CD25+ T cells secreted IL-10 (not IL-2, IL-4 and interferon [IFN]-?), and suppressed secretion of IL-2, IL-4 and IFN-? by CD4+CD25+ T cells in co-culture experiments. Similar characteristics were found in CD4+CD25+ from PBLs, except that these cells produced similar levels of IL-4 when compared with CD4+CD25+ T cells.
This is the first description of regulatory CD4+CD25+ T cells with suppressive functions on CD4+CD25- T cells in humans. One interesting point is that certain differences in cytokine production by CD25+ lymphocytes were found in thymic versus PBL CD4+ T cells. The authors proposed that this could be explained by a difference in the number and/or the type of antigen presenting cells present in these two sites. Another group recently reported the presence of CD4+CD25+ T cells in human PBLs and in tonsils (see Additional information ). They showed that suppression is cell contact dependent, but also demonstrated that it is not mediated via IL-4, IL-10 or transforming growth factor-?. They confirmed that these cells express high levels of CTLA-4. Further characterization of the function and development of these T cells may further our understanding of the cause and mechanism of autoimmune disease, and may help in developing new strategies for treatment.
T cell purification, FACS analysis, co-culture experiments
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