IL-10+CTLA-4+ Th2 Inhibitory Cells Form in a Foxp3-Independent, IL-2-Dependent Manner from Th2 Effectors during Chronic Inflammation
IL-10+CTLA-4+ Th2 Inhibitory Cells Form in a Foxp3-Independent, IL-2-Dependent Manner from Th2 Effectors during Chronic Inflammation
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DOI：
10.4049/jimmunol.1102994
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发表时间：
2012-06-01
影响因子：
4.4
通讯作者：
Cook, Matthew C.
中科院分区：
文献类型：
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作者：
Altin, John A.;Goodnow, Chris C.;Cook, Matthew C.
活化的Th细胞通过正反馈回路影响其他T细胞，这些正反馈回路扩大和抑制特定类型的反应，但关于它们如何也可以启动针对免疫病理反应的负反馈知之甚少。在这项研究中，我们证明了在慢性炎症过程中出现的加塔-3（+）Th 2抑制（Th 2 i）细胞，表达高水平的抑制蛋白，包括IL-10，CTLA-4，和颗粒酶B，但这样做独立于Foxp 3。尽管其他Th 2效应物促进幼稚T细胞的增殖和IL-4产生，但Th 2 i细胞抑制增殖和IL-4产生。我们表明，Th 2 i细胞直接从Th 2效应细胞中发育，其方式可以通过效应细胞因子（包括IL-2，IL-10和IL-21）体外促进，并且需要通过体内CD 28，Card 11和IL-2激活T细胞。Th 2 i细胞的形成可以作为针对过度或慢性Th 2应答的内置激活诱导的反馈抑制机制。免疫学杂志，2012，188：5478-5488。
Activated Th cells influence other T cells via positive feedback circuits that expand and polarize particular types of response, but little is known about how they may also initiate negative feedback against immunopathological reactions. In this study, we demonstrate the emergence, during chronic inflammation, of GATA-3(+) Th2 inhibitory (Th2i) cells that express high levels of inhibitory proteins including IL-10, CTLA-4, and granzyme B, but do so independently of Foxp3. Whereas other Th2 effectors promote proliferation and IL-4 production by naive T cells, Th2i cells suppress proliferation and IL-4 production. We show that Th2i cells develop directly from Th2 effectors, in a manner that can be promoted by effector cytokines including IL-2, IL-10, and IL-21 ex vivo and that requires T cell activation through CD28, Card11, and IL-2 in vivo. Formation of Th2i cells may act as an inbuilt activation-induced feedback inhibition mechanism against excessive or chronic Th2 responses. The Journal of Immunology, 2012, 188: 5478-5488.