| Autor: |
Takeuchi, Arata, Badr, Mohamed El Sherif Gadelhaq, Miyauchi, Kosuke, Ishihara, Chitose, Onishi, Reiko, Guo, Zijin, Sasaki, Yoshiteru, Ike, Hiroshi, Takumi, Akiko, Tsuji, Noriko M., Murakami, Yoshinori, Katakai, Tomoya, Kubo, Masato, Saito, Takashi |
| Zdroj: |
The Journal of Experimental Medicine; January 2016, Vol. 213 Issue: 1 p123-138, 16p |
| Abstrakt: |
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. |
| Databáze: |
Supplemental Index |
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