In the absence of IL-12, CD4+ T cell responses to intracellular pathogens fail to default to a Th2 pattern and are host protective in an IL-10-/- setting
In the absence of IL-12, CD4+ T cell responses to intracellular pathogens fail to default to a Th2 pattern and are host protective in an IL-10-/- setting
复制标题
DOI：
10.1016/s1074-7613(02)00278-9
复制
发表时间：
2002-03-01
期刊：
影响因子：
32.4
通讯作者：
Sher, A
中科院分区：
文献类型：
--
作者：
Jankovic, D;Kullberg, MC;Sher, A
与野生型动物相比，IL-12缺陷型小鼠经历了细胞内病原体的非致死感染或用病原体提取物反复免疫的IL-thema（+）CD4（+）T细胞反复免疫。此外，这些基因敲除动物中的CD4（+）反应未能默认为TH2模式。发现在IL-12缺陷型环境中发育的Th1细胞的保护功效受到IL-10的限制，因为小鼠双重缺乏IL-10和IL-12的缺乏，而IL-12的生存得以幸存，而仅缺乏IL-12的动物屈服于病原体。挑战。与IL-12敲除小鼠相反，暴露于Th1微生物刺激的MyD88缺陷动物产生了纯Th2反应，认为该信号传导元件在确定病原体诱导的CD4极化方面起着比IL-12的关键功能。
IL-12-deficient mice exposed to nonlethal infections with intracellular pathogens or repeatedly immunized with a pathogen extract developed lowered but nevertheless substantial numbers of IFN-gamma(+) CD4(+) T cells compared to those observed in wild-type animals. Moreover, the CD4(+) responses in these knockout animals failed to default to a Th2 pattern. The protective efficacy of the Th1 cells developing in an IL-12-deficient setting was found to be limited by IL-10 since mice doubly deficient in IL-10 and IL-12 survived, while animals deficient in IL-12 alone succumbed to pathogen challenge. In contrast to IL-12 knockout mice, MyD88-deficient animals exposed to a Th1 microbial stimulus developed a pure Th2 response, arguing that this signaling element plays a more critical function than IL-12 in determining pathogen-induced CD4 polarization.