Saraiva Margarida, Christensen Jillian R, Veldhoen Marc, Murphy Theresa L, Murphy Kenneth M, O'Garra Anne
Division of Immunoregulation, MRC National Institute for Medical Research, The Ridgeway, London NW7 1AA, UK.
Immunity. 2009 Aug 21;31(2):209-19. doi: 10.1016/j.immuni.2009.05.012. Epub 2009 Jul 30.
CD4(+) T cells producing interleukin-10 (IL-10) and interferon-gamma (IFN-gamma) are reported in chronic infections. However, the signals that direct the development of IL-10-producing T helper 1 (Th1) cells are undefined. We showed that development of IL-10-producing Th1 cells required high T cell receptor (TCR) ligation, sustained ERK1 and ERK2 MAP kinases phosphorylation, and IL-12-induced STAT4 transcription factor activation. Repeated TCR triggering led to enhanced IL-10 production by Th1 cells, and continued IL-12 action and high-dose TCR signaling were required for the development and maintenance of IL-10-producing Th1 cells. Although Th1, Th2, and Th17 cells require the activation of distinct STATs for their differentiation, activation of ERK1 and ERK2 was a common requirement for production of IL-10 by all Th cell subsets. IL-10 expression also correlated with c-maf expression. Despite having distinct functions in protection against pathogens, all Th cells share the important task of controlling overexuberant immune responses by means of IL-10 production.
据报道，慢性感染中存在产生白细胞介素-10（IL-10）和干扰素-γ（IFN-γ）的CD4(+) T细胞。然而，指导产生IL-10的辅助性T细胞1（Th1）细胞发育的信号尚不清楚。我们发现，产生IL-10的Th1细胞的发育需要高亲和力的T细胞受体（TCR）连接、持续的ERK1和ERK2丝裂原活化蛋白激酶磷酸化以及IL-12诱导的STAT4转录因子激活。重复的TCR触发导致Th1细胞产生的IL-10增加，并且产生IL-10的Th1细胞的发育和维持需要持续的IL-12作用和高剂量的TCR信号。虽然Th1、Th2和Th17细胞在分化过程中需要不同的信号转导和转录激活因子（STAT）激活，但ERK1和ERK2的激活是所有Th细胞亚群产生IL-10的共同要求。IL-10的表达也与c-maf的表达相关。尽管在抵御病原体方面具有不同的功能，但所有Th细胞都通过产生IL-10来共同承担控制过度免疫反应这一重要任务。
