Evidence for down-regulation of highly expressed TCR by CD4 and CD45 on non-selected CD4+CD8+thymocytes |
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Authors: | Sato Takehito; Hozumi Katsuto; Kishihara Kenji; Kametani Yoshie; Sato Chiharu; Kumagai Yoshihiro; Mak Tak W; Habu Sonoko |
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Institution: | Department of Immunology, Tokai University School of Medicine Bohseidai, Isehara, Kanagawa 259-11, Japan
1 Department of Immunology, Medical Institute of Bioregulation, Kyusyu University 3-1-1 Maidashi, Higashi-ku, Fukuoks 812, Japan
2 Inheritance and variation PRESTO, JRDC, 1 Taya-cho, Sakae-ku, Yokohama 244, Kanagawa, Japan
3 The Amgen Institute and Ontario Cancer Institute, Department of Medical Biophysics and Immunology, University of Tront Toronto, Ontario M4X 1K9, Canada |
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Abstract: | Immature CD4+CD8+ double-positive (DP) thymocytes are positivelyselected for further development if they express TCR reactingwith thymic ligands of low affinity. However, the majority ofDP thymocytes express low TCR levels. This low level of TCRmay be insufficient to recognize thymic ligands. To understandthe basis for the low expression of TCR on DP thymocytes, wedetermined the density of TCR expression at various stages oftheir development using TCR transgenic (TCR-Tg) mice. We foundthat TCR expression was high in the thymocytes that had recentlytransited into the DP stage but then gradually decreased onDP cells if they were not selected by TCR interaction with MHCmolecules. However, such TCR suppression was not observed inpositively selected DP cells and in the non-selected DP cellsobtained from CD45 deficient mice or from mice receiving anti-CD4mAb. These findings suggest that the once highly expressed TCRat the DP stage is suppressed by CD45 and/or CD4 on non-selectedthymocytes. Furthermore, TCR suppression is prevented by TCR-mediatedsignals. The maintenance of high TCR levels on positively selectedDP thymocytes may facilitate their selection. |
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Keywords: | positive selection TCR transgenic mouse |
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