OX40 ligand shuts down IL-10-producing regulatory T cells
OX40 ligand shuts down IL-10-producing regulatory T cells
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DOI：
10.1073/pnas.0603107103
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发表时间：
2006-08-29
影响因子：
11.1
通讯作者：
Liu, Yong-Jun
中科院分区：
文献类型：
--
作者：
Ito, Tomoki;Wang, Yui-Hsi;Liu, Yong-Jun
产生IL-10的CD4(+)1型调节性T细胞(TR1)在维持外周免疫耐受中起着关键作用。虽然免疫抑制药物、细胞因子、共刺激分子和未成熟的树突状细胞参与了TO细胞的诱导，但对TO细胞的产生和功能进行负面调节的信号一直难以捉摸。我们报道了OX40配体(OX40L)完全抑制免疫抑制药物地塞米松和维生素D3诱导的幼稚和记忆性CD4+T细胞产生IL-10。OX40L的这一独特功能不被GITR配体和4-1BB配体这两个共刺激因子家族成员所共享。OX40L强烈抑制共刺激配体和未成熟树突状细胞两种生理刺激诱导的细胞产生IL-10。此外，OX40L还强烈抑制IL-10的产生，并抑制细胞分化产生IL-10的功能。OX40L的这两个新功能揭示了OX40/OX40L调节免疫和耐受的机制。
IL-10-producing CD4(+) type 1 regulatory T (Tr1) cells play a critical role in the maintenance of peripheral tolerance. Although immunosuppressive drugs, cytokines, costimulatory molecules, and immature dendritic cells are implicated in the induction of TO cells, the signals that negatively regulate the generation and function of TO cells have been elusive. We report that OX40 ligand (OX40L) completely inhibited the generation of IL-10-producing TO cells from naive and memory CD4+ T cells induced by the immunosuppressive drugs dexamethasone and vitamin D3. This unique function of OX40L was not shared by two costimulatory TNF family members, GITR ligand and 4-1BB ligand. OX40L strongly inhibited the generation of IL-10-producing TO cells induced by two physiologic stimuli, the inducible costimulatory ligand and immature dendritic cells. In addition, OX40L strongly inhibited IL-10 production and suppressive function of differentiated IL-10-producing TO cells. These two novel functions of OX40L shed light on the mechanism by which OX40/OX40L regulates immunity and tolerance.