IL-10 induces regulatory T cell apoptosis by up-regulation of the membrane form of TNF-α
IL-10 induces regulatory T cell apoptosis by up-regulation of the membrane form of TNF-α
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DOI：
10.4049/jimmunol.172.2.1028
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发表时间：
2004-01-15
影响因子：
4.4
通讯作者：
Zhang, L
中科院分区：
文献类型：
--
作者：
Marra, LE;Zhang, ZX;Zhang, L
大量研究证明了调节性 T (Treg) 细胞在外周耐受中的作用。然而，如何控制 Treg 细胞的生存和死亡在很大程度上尚不清楚。在这项研究中，我们研究了调节Ag特异性alphaTCR(+) CD4(-)CD8(-)双阴性(DN) Treg细胞亚群稳态的机制。我们证明 DN Treg 细胞天然抵抗 TCR 交联诱导的细胞凋亡。给予外源性 IL-10 使 DN Treg 细胞易于凋亡，并消除其抑制功能。此外，在 IL-10 存在的情况下，DN Treg 细胞的 TCR 交联会导致膜结合形式的 TNF-α 上调，但不会导致可溶形式的 TNF-α 上调。膜结合的 TNF-α 与 TNFR2 的相互作用向 DN Treg 细胞发送死亡信号。阻止它们的相互作用可以逆转效果。 DN Treg 细胞上的 IL-10。这些结果提供了对调节 DN Treg 细胞功能和稳态的机制的见解。
Numerous studies have demonstrated the role of regulatory T (Treg) cells in peripheral tolerance. Nevertheless, how the survival and death of Treg cells is controlled is largely unknown. In this study, we investigated the mechanisms involved in regulating the homeostasis of a subset of Ag-specific alphabetaTCR(+) CD4(-)CD8(-) double negative (DN) Treg cells. We demonstrate that DN Treg cells are naturally resistant to TCR cross-linking-induced apoptosis. Administration of exogenous IL-10 renders DN Treg cells susceptible to apoptosis, and abolishes their suppressive function. Furthermore, TCR cross-linking of DN Treg cells in the presence of IL-10 leads to the up-regulation of the membrane-bound but not the soluble form of TNF-alpha. Interaction of membrane bound TNF-a with TNFR2 sends death signals to DN Treg cells. Blocking their interaction can reverse the effects. of IL-10 on DN Treg cells. These results provide insights into the mechanisms that regulate the function and homeostasis of DN Treg cells.