细胞毒性T细胞
生物
CD8型
T细胞
谱系(遗传)
T细胞受体
主要组织相容性复合体
细胞命运测定
细胞生物学
获得性免疫系统
基因
免疫系统
遗传学
转录因子
体外
作者
Miho Shinzawa,E. Ashley Moseman,Selamawit Gossa,Yasuko Mano,Abhisek Bhattacharya,Terry I. Guinter,Amala Alag,Xiongfong Chen,Maggie Cam,Dorian B. McGavern,Batu Erman,Alfred Singer
标识
DOI:10.1038/s41590-022-01187-1
摘要
Abstract T cell specificity and function are linked during development, as MHC-II-specific TCR signals generate CD4 helper T cells and MHC-I-specific TCR signals generate CD8 cytotoxic T cells, but the basis remains uncertain. We now report that switching coreceptor proteins encoded by Cd4 and Cd8 gene loci functionally reverses the T cell immune system, generating CD4 cytotoxic and CD8 helper T cells. Such functional reversal reveals that coreceptor proteins promote the helper-lineage fate when encoded by Cd4 , but promote the cytotoxic-lineage fate when encoded in Cd8 —regardless of the coreceptor proteins each locus encodes. Thus, T cell lineage fate is determined by cis -regulatory elements in coreceptor gene loci and is not determined by the coreceptor proteins they encode, invalidating coreceptor signal strength as the basis of lineage fate determination. Moreover, we consider that evolution selected the particular coreceptor proteins that Cd4 and Cd8 gene loci encode to avoid generating functionally reversed T cells because they fail to promote protective immunity against environmental pathogens.
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