Inducible costimulator protein (ICOS) controls T helper cell subset polarization after virus and parasite infection.

Inducible costimulator protein (ICOS) controls T helper cell subset polarization after virus and parasite infection.
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DOI:
10.1084/jem.192.1.53
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发表时间:
2000-07-03
期刊:
The Journal of experimental medicine
影响因子:
--
通讯作者:
Bachmann MF
Bachmann MF
中科院分区:
其他
文献类型:
--
作者:
Kopf M;Coyle AJ;Schmitz N;Barner M;Oxenius A;Gallimore A;Gutierrez-Ramos JC;Bachmann MF

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研究表明,某些病原体可以在缺乏CD28的情况下触发有效的T细胞反应,CD28是静止T细胞上表达的一种关键共刺激受体。诱导共刺激蛋白(Inducible costimulator protein, ICOS)是一种与CD28在结构和功能上相关的诱导共刺激蛋白。在缺乏CD28的情况下,T辅助细胞1型(Th1)和Th2反应在感染淋巴细胞性脉络丛脑膜炎病毒(LCMV)、水疱性口炎病毒(VSV)和巴西尼波圆线虫后受到损害,但并未完全消除。抑制cd28缺陷小鼠的ICOS进一步降低了Th1/Th2极化。单独阻止ICOS具有有限但重要的下调Th子集发展的能力。相比之下,细胞毒性T淋巴细胞(CTL)反应(分别在LCMV和VSV感染后由CD28在较小和较大程度上调节)不受ICOS阻断的影响。总之,我们的研究结果表明,ICOS在体内调节cd28依赖性和cd28非依赖性CD4+亚群(Th1和Th2)反应,但不调节CTL反应。
It has been shown that certain pathogens can trigger efficient T cell responses in the absence of CD28, a key costimulatory receptor expressed on resting T cells. Inducible costimulator protein (ICOS) is an inducible costimulator structurally and functionally related to CD28. Here, we show that in the absence of CD28 both T helper cell type 1 (Th1) and Th2 responses were impaired but not abrogated after infection with lymphocytic choriomeningitis virus (LCMV), vesicular stomatitis virus (VSV), and the nematode Nippostrongylus brasiliensis. Inhibition of ICOS in CD28-deficient mice further reduced Th1/Th2 polarization. Blocking of ICOS alone had a limited but significant capacity to downregulate Th subset development. In contrast, cytotoxic T lymphocyte (CTL) responses, which are regulated to a minor and major extent by CD28 after LCMV and VSV infection, respectively, remained unaffected by blocking ICOS. Together, our results demonstrate that ICOS regulates both CD28-dependent and CD28-independent CD4+ subset (Th1 and Th2) responses but not CTL responses in vivo.
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