Division of Infectious Diseases, Department of Medicine, Chang Gung Memorial Hospital, Chang Gung University, Kweishan, Taoyuan 33333, Taiwan.
Department of Pathology, Chang Gung Memorial Hospital, Chang Gung University, Kweishan, Taoyuan 33333, Taiwan.
Nat Commun. 2015 Mar 2;6:6374. doi: 10.1038/ncomms7374.
Th1 cells control their activity by producing regulatory IL-10. Here we report that Th1 cell-derived IL-10 facilitates their expansion and, in addition, augments Th1 cell production of IFN-γ, TNF-α and IL-2 during the early phase of influenza. In our antigen-specific mouse experimental system, influenza haemagglutinin-specific CD4(+) T cells respond to infection with the induction of T-bet, and produce both IFN-γ and IL-10. In the early phase of infection, an abundance of viral neuraminidase causes TGF-β activation of haemagglutinin-specific CD4(+) T cells. CD4(+) T-cell-derived IL-10 inhibits neuraminidase-driven TGF-β activation and counteracts the virus-mediated immune suppression. As the host eradicates the virus, neuraminidase activity wanes and IL-10 receptors are upregulated on CD4(+) T cells in the late phase of infection. IL-10 then suppresses immune activation and aids in recovery from infection and inflammation. These results reveal a previously unrecognized function of Th1 cell-derived IL-10 in vivo.
Th1 细胞通过产生调节性的 IL-10 来控制其活性。在这里，我们报告 Th1 细胞衍生的 IL-10 促进了它们的扩增，并且在流感的早期阶段还增强了 Th1 细胞 IFN-γ、TNF-α 和 IL-2 的产生。在我们的抗原特异性小鼠实验系统中，流感血凝素特异性 CD4(+)T 细胞对感染的反应是诱导 T-bet，并产生 IFN-γ 和 IL-10。在感染的早期阶段，大量的病毒神经氨酸酶导致 TGF-β 激活血凝素特异性 CD4(+)T 细胞。CD4(+)T 细胞衍生的 IL-10 抑制神经氨酸酶驱动的 TGF-β 激活，并对抗病毒介导的免疫抑制。随着宿主消灭病毒，神经氨酸酶活性在感染后期减弱，IL-10 受体在 CD4(+)T 细胞上上调。IL-10 随后抑制免疫激活，并有助于从感染和炎症中恢复。这些结果揭示了 Th1 细胞衍生的 IL-10 在体内的一个以前未被认识到的功能。
