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
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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