Regulatory and effector T cell activation levels are prime determinants of in vivo immune regulation

被引:61
作者
Billiard, Fabienne [1 ]
Litvinova, Elena [1 ]
Saadoun, David [1 ]
Djelti, Fathia [1 ]
Klatzmann, David [1 ]
Cohen, Jose L. [1 ]
Marodon, Gilles [1 ]
Salomon, Benoit L. [1 ]
机构
[1] Univ Paris 06, CNRS, UMR 7087, Hop La Pitie Salpetriere, F-75013 Paris, France
关键词
D O I
10.4049/jimmunol.177.4.2167
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Little is known about the in vivo conditions in which CD4(+)CD25(+) regulatory T cells (T,,g) exert their suppressive effect in nonlymphopenic mice. To this end, we analyzed T-reg-mediated suppression of expansion and cytokine production at different levels of Ag-specific CD4(+)CD25(-) T cell activation. Using Ab-mediated depletion of endogenous T-reg, we show that basal immunosuppression is dependent on effector T cell activation. These polyclonal T-reg, which were poorly activated in our immunization conditions, were effective in weak but not high T cell activation context. In contrast, the same immunization conditions led to proliferation of cotransferred Ag-specific T-reg. Those efficiently inhibited T cell proliferation and cytokine production even in strong T cell activation context. Interestingly, T-reg selectively suppressed expansion or cytokine production depending on the experimental approach. The importance of the immune context for efficient suppression is further supported by the observation that T-reg depletion exacerbated diabetes of NOD mice only at the early stage of the disease. Overall, our study suggests that T-reg-mediated suppression depends on the relative activation of T-reg and effector T cells in vivo. This balance may be a critical factor in the regulation of immune responses.
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收藏
页码:2167 / 2174
页数:8
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