CRTAM determines the CD4+ cytotoxic T lymphocyte lineage

细胞毒性T细胞 CTL公司* 生物 穿孔素 颗粒酶 CD8型 细胞生物学 白细胞介素21 颗粒酶A 颗粒酶B 免疫学 分子生物学 免疫系统 体外 生物化学
作者
Arata Takeuchi,Mohamed El Sherif Gadelhaq Badr,Kosuke Miyauchi,Chitose Ishihara,Reiko Onishi,Zijin Guo,Yoshiteru Sasaki,H. Ike,Akiko Takumi,Noriko M. Tsuji,Yoshinori Murakami,Tomoya Katakai,Masato Kubo,Takashi Saito
出处
期刊:Journal of Experimental Medicine [Rockefeller University Press]
卷期号:213 (1): 123-138 被引量:172
标识
DOI:10.1084/jem.20150519
摘要

Naive T cells differentiate into various effector T cells, including CD4+ helper T cell subsets and CD8+ cytotoxic T cells (CTL). Although cytotoxic CD4+ T cells (CD4+CTL) also develop from naive T cells, the mechanism of development is elusive. We found that a small fraction of CD4+ T cells that express class I–restricted T cell–associated molecule (CRTAM) upon activation possesses the characteristics of both CD4+ and CD8+ T cells. CRTAM+ CD4+ T cells secrete IFN-γ, express CTL-related genes, such as eomesodermin (Eomes), Granzyme B, and perforin, after cultivation, and exhibit cytotoxic function, suggesting that CRTAM+ T cells are the precursor of CD4+CTL. Indeed, ectopic expression of CRTAM in T cells induced the production of IFN-γ, expression of CTL-related genes, and cytotoxic activity. The induction of CD4+CTL and IFN-γ production requires CRTAM-mediated intracellular signaling. CRTAM+ T cells traffic to mucosal tissues and inflammatory sites and developed into CD4+CTL, which are involved in mediating protection against infection as well as inducing inflammatory response, depending on the circumstances, through IFN-γ secretion and cytotoxic activity. These results reveal that CRTAM is critical to instruct the differentiation of CD4+CTL through the induction of Eomes and CTL-related gene.
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