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Abstract
You Jeong Lee1,2, Yoon Kyung Jeon1, Byung Hyun Kang5, Doo Hyun Chung1, Chung-Gyu Park3, Hee Young Shin4, Kyeong Cheon Jung1,2, and Seong Hoe Park1,2
1 Department of Pathology, 2 Department of Immunology, 3 Department of Microbiology, and 4 Department of Pediatrics and Adolescent Medicine, Seoul National University College of Medicine, Seoul 110-799, Korea
5 Department of Biomedical Sciences, Seoul National University Graduate School, Seoul 110-799, Korea
CORRESPONDENCE Seong Hoe Park
Human thymocytes, unlike mouse thymocytes, express major histocompatibility complex (MHC) class II molecules on their surface, especially during the fetal and perinatal stages. Based on this observation, we previously identified a novel developmental pathway for the generation of CD4+ T cells via interactions between MHC class II-expressing thymocytes (thymocyte-thymocyte [T-T] interactions) with a transgenic mouse system. However, the developmental dissection of this T-T interaction in humans has not been possible because of the lack of known cellular molecules specific for T-T CD4+ T cells. We show that promyelocytic leukemia zinc finger protein (PLZF) is a useful marker for the identification of T-T CD4+ T cells. With this analysis, we determined that a substantial number of fetal thymocytes and splenocytes express PLZF and acquire innate characteristics during their development in humans. Although these characteristics are quite similar to invariant NKT (iNKT) cells, they clearly differ from iNKT cells in that they have a diverse T cell receptor repertoire and are restricted by MHC class II molecules. These findings define a novel human CD4+ T cell subset that develops via an MHC class II-dependent T-T interaction.
Y.J. Lee and Y.K. Jeon contributed equally to this paper.
Abbreviations used: αGalCer, α-galactosylceramide; DP, double positive; hu-mice, humanized mice; GA, gestational age; iNKT, invariant NKT; MAIT, mucosal-associated invariant T; NOG, NOD.SCID/γc-/-; pIV, CIITA type IV promoter; PLZF, promyelocytic leukemia zinc finger protein; SLAM, signaling lymphocytic activation molecule; SP, single positive; T-E, thymocyte-epithelial cell; T-T, thymocyte-thymocyte.
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