Differential Responsiveness of Innate-like IL-17-and IFN-β-Producing γδ T Cells to Homeostatic Cytokines
Differential Responsiveness of Innate-like IL-17-and IFN-β-Producing γδ T Cells to Homeostatic Cytokines
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DOI：
10.4049/jimmunol.1502082
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发表时间：
2016-01-15
影响因子：
4.4
通讯作者：
Webster, Kylie E.
中科院分区：
文献类型：
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作者：
Corpuz, Theresa M.;Stolp, Jessica;Webster, Kylie E.
γ δ T细胞使用TCR和非TCR分子对感染或细胞应激后上调的分子作出应答。先天性信号相对于TCR连接的重要性变化很大。产生γ δ T（γ δ T-17）和产生IFN-γ的γ δ T（γ δ T-IFN γ）的先天样IL-17亚群在胸腺发育后调节其TCR的敏感性，从而允许对外周中的炎性细胞因子的强烈应答。剩余的常规γ δ T细胞保持高TCR应答性。我们确定了在外周淋巴组织中控制这些不同亚群的稳态机制。我们发现，虽然先天性γ δ T-17和γ δ T-IFN γ细胞共享胸腺发育的元素，但它们在稳态方面存在分歧。与传统的γ δ T细胞相比，两者都表现出对细胞因子的急性敏感性，但它们不垄断相同的细胞因子。γ δ T-17细胞完全依赖于IL-7的周转和存活，使它们与NKT 17细胞对齐; IL-7连接触发增殖，以及促进存活，上调Bcl-2和Bcl-x（L）。γ δ T-IFN γ细胞反而严重依赖于IL-15。它们表现出类似于记忆性CD 8（+）T细胞的特性，并在细胞因子刺激时上调Bcl-x（L）和Mcl-1。常规的γ δ Τ细胞显示出对单独的精氨酸刺激的低敏感性，并且有利于IL-7的周转，这一特征使人联想到幼稚α β Τ细胞，表明它们也可能需要强直性TCR信号传导用于群体维持。这些生存限制表明，γ δ T细胞亚群不直接相互竞争细胞因子，而是与其他功能相似的淋巴细胞落入资源小生境。
gamma delta T cells respond to molecules upregulated following infection or cellular stress using both TCR and non-TCR molecules. The importance of innate signals versus TCR ligation varies greatly. Both innate-like IL-17-producing gamma delta T (gamma delta T-17) and IFN-gamma-producing gamma delta T (gamma delta T-IFN gamma) subsets tune the sensitivity of their TCR following thymic development, allowing robust responses to inflammatory cytokines in the periphery. The remaining conventional gamma delta T cells retain high TCR responsiveness. We determined homeostatic mechanisms that govern these various subsets in the peripheral lymphoid tissues. We found that, although innate-like gamma delta T-17 and gamma delta T-IFN gamma cells share elements of thymic development, they diverge when it comes to homeostasis. Both exhibit acute sensitivity to cytokines compared with conventional gamma delta T cells, but they do not monopolize the same cytokine. gamma delta T-17 cells rely exclusively on IL-7 for turnover and survival, aligning them with NKT17 cells; IL-7 ligation triggers proliferation, as well as promotes survival, upregulating Bcl-2 and Bcl-x(L). gamma delta T-IFN gamma cells instead depend heavily on IL-15. They display traits analogous to memory CD8(+) T cells and upregulate Bcl-x(L) and Mcl-1 upon cytokine stimulation. The conventional gamma delta T cells display low sensitivity to cytokine-alone stimulation and favor IL-7 for their turnover, characteristics reminiscent of naive alpha beta T cells, suggesting that they may also require tonic TCR signaling for population maintenance. These survival constraints suggest that gamma delta T cell subsets do not directly compete with each other for cytokines, but instead fall into resource niches with other functionally similar lymphocytes.