Differential Requirements for Th1 and Th17 Responses to a Systemic Self-Antigen
Differential Requirements for Th1 and Th17 Responses to a Systemic Self-Antigen
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DOI：
10.4049/jimmunol.1003786
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发表时间：
2011-04-15
影响因子：
4.4
通讯作者：
Abbas, Abul K.
中科院分区：
文献类型：
--
作者：
Katzman, Shoshana D.;Gallo, Eugenio;Abbas, Abul K.
T细胞与APC的相互作用对于启动针对外来抗原和自身抗原的效应性反应是必不可少的，但这些相互作用在体内产生不同群体的效应性T细胞中的作用尚不清楚。使用一个没有佐剂或感染的CD4(+)T细胞对系统自身抗原的反应模型，我们证明了APC的激活对Th17反应的增强作用远远大于Th1反应。对系统抗原的识别可诱导自身反应性CD4(+)T细胞的耐受，但即使在产生耐受的条件下，CD40信号的诱导也会导致强烈的、抗原特异性的IL-17反应，而不会产生大量产生干扰素-γ的细胞。将相同的CD4(+)T细胞转移到表达自身抗原的淋巴细胞减少的接受者体内，会导致IL-17、干扰素-γ的不受控制的产生，并导致全身炎症。如果抗原特异性T细胞缺乏CD40L，则IL-17的产生减少，而不是干扰素-γ的产生，并显著延长受体小鼠的存活时间。此外，瞬时阻断最初依赖MHC II类的T细胞与APC的相互作用会导致IL-17的减少，而不是干扰素-γ的产生。这些数据表明，Th17的分化对T细胞与APC的相互作用比Th1反应更敏感，而阻断这种相互作用，特别是CD40途径，可能是控制Th17介导的自身免疫的关键。免疫学杂志，2011,186：4668-4673。
T cell-APC interactions are essential for the initiation of effector responses against foreign and self-antigens, but the role of these interactions in generating different populations of effector T cells in vivo remains unclear. Using a model of CD4(+) T cell responses to a systemic self-antigen without adjuvants or infection, we demonstrate that activation of APCs augments Th17 responses much more than Th1 responses. Recognition of systemic Ag induces tolerance in self-reactive CD4(+) T cells, but induction of CD40 signaling, even under tolerogenic conditions, results in a strong, Ag-specific IL-17 response without large numbers of IFN-gamma-producing cells. Transfer of the same CD4(+) T cells into lymphopenic recipients expressing the self-antigen results in uncontrolled production of IL-17, IFN-gamma, and systemic inflammation. If the Ag-specific T cells lack CD40L, production of IL-17 but not IFN-gamma is decreased, and the survival time of recipient mice is significantly increased. In addition, transient blockade of the initial MHC class II-dependent T cell-APC interaction results in a greater reduction of IL-17 than of IFN-gamma production. These data suggest that Th17 differentiation is more sensitive to T cell interactions with APCs than is the Th1 response, and interrupting this interaction, specifically the CD40 pathway, may be key to controlling Th17-mediated autoimmunity. The Journal of Immunology, 2011, 186: 4668-4673.