Microbial infection-induced expansion of effector T cells overcomes the suppressive effects of regulatory T cells via an IL-2 deprivation mechanism.
Microbial infection-induced expansion of effector T cells overcomes the suppressive effects of regulatory T cells via an IL-2 deprivation mechanism.
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DOI：
10.4049/jimmunol.1100769
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发表时间：
2012-01-15
期刊：
影响因子：
--
通讯作者：
Yarovinsky F
中科院分区：
文献类型：
--
作者：
Benson A;Murray S;Divakar P;Burnaevskiy N;Pifer R;Forman J;Yarovinsky F
调节性Foxp3+T细胞是一种重要的细胞群，可抑制T细胞对微生物和病毒病原体的激活。在弓形虫、单核细胞增生性李斯特氏菌和痘苗病毒这三种不同的感染背景下，我们确定了一种细胞内在机制，即效应器CD4+T细胞克服Treg细胞的抑制作用。对寄生虫、细菌和病毒病原体的急性反应导致Treg细胞的频率和绝对数量一过性下降。感染诱导的Treg细胞的部分丢失对于启动有效的Th1反应和宿主对病原体的保护是必不可少的。观察到的Treg细胞的消失是由于病原体特异性的CD4+T细胞的扩增导致IL-2不足所致，而产生IL-2的能力有限。在寄生虫、细菌和病毒感染期间，外源性IL-2治疗完全防止Treg细胞的丢失，但Treg细胞的恢复导致对病原体的敏感性大大增强。这些结果表明，病原体通过剥夺IL-2诱导的Treg细胞的瞬时减少对于最佳的T细胞反应和宿主对微生物和病毒病原体的抵抗力是必不可少的。
Regulatory Foxp3+ T cells are a critical cell population that suppresses T cell activation in response to microbial and viral pathogens. We identify a cell-intrinsic mechanism by which effector CD4+ T cells overcome the suppressive effects of Treg cells in the context of three distinct infections, Toxoplasma gondii, Listeria monocytogenes, and vaccinia virus. The acute responses to the parasitic, bacterial, and viral pathogens resulted in a transient reduction in frequency and absolute number of Treg cells. The infection-induced partial loss of Treg cells was essential for the initiation of potent Th1 responses and for host protection against the pathogens. The observed disappearance of Treg cells was a result of insufficiency in IL-2 caused by the expansion of pathogen-specific CD4+ T cells with a limited capacity of IL-2 production. Exogenous IL-2 treatment during the parasitic, bacterial, and viral infections completely prevented the loss of Treg cells, but restoration of Treg cells resulted in a greatly enhanced susceptibility to the pathogens. These results demonstrate that the transient reduction in Treg cells induced by pathogens via IL-2 deprivation is essential for optimal T cell responses and for host resistance to microbial and viral pathogens.
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影响因子：
30.3
作者：
Benson A;Pifer R;Behrendt CL;Hooper LV;Yarovinsky F
通讯作者：
Yarovinsky F
DOI：
10.4049/jimmunol.1000423
发表时间：
2010-08-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Fulton RB;Meyerholz DK;Varga SM
通讯作者：
Varga SM
影响因子：
4.4
作者：
Andersson, J;Boasso, A;Chougnet, CA
通讯作者：
Chougnet, CA
影响因子：
15.9
作者：
Abdollahi-Roodsaz, Shahla;Joosten, Leo A. B.;Van den Berg, Wim B.
通讯作者：
Van den Berg, Wim B.
影响因子：
82.9
作者：
Hisaeda, H;Maekawa, Y;Yasutomo, K
通讯作者：
Yasutomo, K