Cutting Edge: Helminth Coinfection Blocks Effector Differentiation of CD8 T Cells through Alternate Host Th2- and IL-10-Mediated Responses.
Cutting Edge: Helminth Coinfection Blocks Effector Differentiation of CD8 T Cells through Alternate Host Th2- and IL-10-Mediated Responses.
复制标题
DOI：
10.4049/jimmunol.1601741
复制
发表时间：
2017-01-15
期刊：
影响因子：
--
通讯作者：
Yap GS
中科院分区：
文献类型：
--
作者：
Marple A;Wu W;Shah S;Zhao Y;Du P;Gause WC;Yap GS
并发蠕虫感染有效地抑制T细胞免疫;然而，蠕虫是否阻止T细胞引发或偏斜克隆募集和效应分化尚不清楚。使用两种天然小鼠病原体多回Heligsomosoides和弓形虫共感染来研究蠕虫对CD 8 T细胞反应的负面影响，我们证明了蠕虫诱导的KLRG 1+效应CD 8 T细胞IL-12依赖性分化的抑制和IFNγ的产生。然而，逆转蠕虫对CD 8 α+ DCs的先天性IL-12应答的抑制（发生在STAT 6缺陷小鼠中）不足以使CD 8 T细胞分化正常化。相反，需要IL-4和IL-10的联合缺乏来逆转蠕虫共感染对CD 8 T细胞应答的负面影响。单克隆T.过继转移到共感染小鼠的弓形虫特异性CD 8 T细胞概括了蠕虫诱导的对多克隆CD 8 T应答的影响，表明不需要克隆偏斜。
Concurrent helminth infection potently inhibits T cell immunity; however, whether helminths prevent T cell priming or skew clonal recruitment and effector differentiation is not known. Using coinfection with two natural mouse pathogens, Heligsomosoides polygyrus and Toxoplasma gondii to investigate the negative impact of helminthes on the CD8 T cell response, we demonstrate helminth-induced suppression of IL-12-dependent differentiation of KLRG1+ effector CD8 T cells and IFNγ production. Nevertheless, reversal of helminth suppression of the innate IL-12 response of CD8α+ DCs, which occurred in STAT6-deficient mice, was not sufficient to normalize CD8 T cell differentiation. Instead, a combined deficiency in IL-4 and IL-10 was required to reverse the negative effects of helminth coinfection on the CD8 T cell response. Monoclonal T. gondii-specific CD8 T cells adoptively transferred into coinfected mice recapitulated the spectrum of helminth-induced effects on the polyclonal CD8 T response, indicating the lack of requirement for clonal skewing.