Deviation from a strong Th1-dominated to a modest Th17-dominated CD4 T cell response in the absence of IL-12p40 and type IIFNs sustains protective CD8 T cells
Deviation from a strong Th1-dominated to a modest Th17-dominated CD4 T cell response in the absence of IL-12p40 and type IIFNs sustains protective CD8 T cells
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DOI：
10.4049/jimmunol.180.6.4109
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发表时间：
2008-03-15
影响因子：
4.4
通讯作者：
Way, Sing Sing
中科院分区：
文献类型：
--
作者：
Orgun, Nural N.;Mathis, Meredith A.;Way, Sing Sing
初始CD4 T细胞分化为特定的效应亚群在很大程度上是由细胞因子的环境控制的。驱动新描述的Th17谱系分化的细胞因子已经在体外被表征，但在体内感染反应中对该谱系的主要承诺细胞因子尚不清楚。单核增生李斯特菌（Lm）在野生型小鼠中诱导强烈的Th1反应。相比之下，我们证明在缺乏IL-12p40（或IFN- γ）和I型IFN受体信号的情况下，Th1 ag特异性CD4 T细胞应答实际上被消除，取而代之的是相对低强度的th17主导应答。这种Th17反应依赖于tgf - β和IL-6。尽管CD4 T细胞反应发生了这种变化，但CD4和CD8 T细胞反应的动力学、CD8 T细胞反应的质量以及CD8 T细胞介导保护的能力都没有受到影响。因此，保护性CD8 T细胞免疫的产生对扰动具有弹性，这些扰动取代了th1主导的强大的th17主导的ag特异性CD4 T细胞应答。
The differentiation of naive CD4 T cells into specific effector subsets is controlled in large part by the milieu of cytokines present during their initial encounter with Ag. Cytokines that drive differentiation of the newly described Th17 lineage have been characterized in vitro, but the cytokines that prime commitment to this lineage in response to infection in vivo are less clear. Listeria monocytogenes (Lm) induces a strong Th1 response in wild-type mice. By contrast, we demonstrate that in the absence of IL-12p40 (or IFN-gamma) and type I IFN receptor signaling, the Th1 Ag-specific CD4 T cell response is virtually abolished and replaced by a relatively low magnitude Th17-dominated response. This Th17 response was dependent on TGF-beta and IL-6. Despite this change in CD4 T cell response, neither the kinetics of the CD4 and CD8 T cell responses, the quality of the CD8 T cell response, nor the ability of CD8 T cells to mediate protection were affected. Thus, generation of protective CD8 T cell immunity was resilient to perturbations that replace a strong Th1-dominated to a reduced magnitude Th17-dominated Ag-specific CD4 T cell response.