共 52 条
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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页码:2167 / 2174
页数:8
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