2003 Fiscal Year Final Research Report Summary
Functions of Thymic Epithelial Cells
| Project/Area Number |
14370109
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Immunology
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| Research Institution | The University of Tokyo |
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Principal Investigator |
MIYAJIMA Atsushi THE UNIVERSITY OF TOKYO, INSTITUTE OF MOLECULAR AND CELLULAR BIOSCIENCES, PROFESSOR, 分子細胞生物学研究所, 教授 (50135232)
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| Co-Investigator(Kenkyū-buntansha) |
TANAKA Minoru THE UNIVERSITY OF TOKYO, INSTITUTE OF MOLECULAR AND CELLULAR BIOSCIENCES, Associate Professor, 分子細胞生物学研究所, 助手 (80321909)
SEKINE Keisuke THE UNIVERSITY OF TOKYO, INSTITUTE OF MOLECULAR AND CELLULAR BIOSCIENCES, Associate Professor, 分子細胞生物学研究所, 助手 (00323569)
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| Project Period (FY) |
2002 – 2003
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| Keywords | thymus / macrophage / denritic cells / apoptosis / epithelial cells / T cell / cytokine / antigen |
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| Research Abstract |
During T cell development in the thymus, T cells encounter antigen-presenting cells and are subjected to either positive or negative selection. CD4^+/CD8^+ double positive (DP) cells that recognize major histocompatibility complex (MHC) on the surface of thymic stromal cells survive, whereas those DP cells that do not recognize MHC die by apoptosis. DP cells that respond to self-antigens are also depleted by apoptosis, and then DP cells differentiate to either CD4 or CD8 single positive (SP) cells. Thus, a vast majority of thymocytes is eliminated during T cell development by apoptosis. However, apoptotic thymocytes are not usually found in the thymus, indicating that apoptotic thymocytes must be eliminated rapidly by scavengers. In this study, we found that CD^<4+>/CD11b^+/CD11c^+ cells were present in the thymus and that these CD^<4+>+/CD11b^+ cells phagocytosed apoptotic thymocytes much more efficiently than thymic CD4/CD11b^+ cells as well as activated peritoneal macrophages. CD4^+/CD11b^+ cells became larger along with thymus development, while no such change was observed in CD4^-/CD11b^+ cells. These results strongly suggest that thymic CD4^+/CD11b^+ cells are major scavengers of apoptotic thymocytes. We also found that CD4^+/CD11b^+ cells were derived from the immature thymocytes through the interaction with Oncostatin M (OSM) responsive thymic epithelial cells. Studies on OSMR deficient mice revealed that OSM is important for the thymic development.
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