1. CRTAM determines the CD4+ cytotoxic T lymphocyte lineage
- Author
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Chitose Ishihara, Mohamed E.l.Sherif G.adelhaq Badr, Kosuke Miyauchi, Yoshinori Murakami, Noriko M. Tsuji, Akiko Takumi, Masato Kubo, Tomoya Katakai, Hiroshi Ike, Yoshiteru Sasaki, Takashi Saito, Zijin Guo, Arata Takeuchi, and Reiko Onishi
- Subjects
0301 basic medicine ,CD4-Positive T-Lymphocytes ,T cell ,Immunology ,Eomesodermin ,Immunoglobulins ,chemical and pharmacologic phenomena ,Mice, Transgenic ,Biology ,CD8-Positive T-Lymphocytes ,Article ,Cell Line ,03 medical and health sciences ,Interleukin 21 ,Interferon-gamma ,Mice ,Cell Movement ,T-Lymphocyte Subsets ,medicine ,Immunology and Allergy ,Cytotoxic T cell ,Animals ,Humans ,Research Articles ,Inflammation ,Mice, Knockout ,Mucous Membrane ,hemic and immune systems ,Cell Differentiation ,Colitis ,Cell biology ,Granzyme B ,CTL ,030104 developmental biology ,medicine.anatomical_structure ,Phenotype ,Perforin ,Gene Expression Regulation ,biology.protein ,T-Box Domain Proteins ,CD8 ,T-Lymphocytes, Cytotoxic - Abstract
Takeuchi et al. demonstrate that CRTAM identifies CD4 T cells with cytotoxic function, and present new insights into CD4+CTL development., 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.
- Published
- 2015