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International Immunology, Vol. 11, No. 1, 89-97, January 1999
© 1999 Japanese Society for Immunology

CD45 can act as a negative regulator for the transition from early to late CD4+CD8+ thymocytes

Takehito Sato, Satoshi Nunomura, Chiharu Sato, Katsuto Hozumi, Yoshihiro Kumagai1, Takashi Nishimura, Tak W. Mak2, Kenji Kishihara3 and Sonoko Habu

Department of Immunology, Tokai University School of Medicine, Boseidai, Isehara, Kanagawa 259-11, Japan
1 Inheritance and Variation, PRESTO, JRDC, Taya-cho, Sakae-ku, Yokohama, Kanagawa 244, Japan
2 The Amgen Institute and Ontario Cancer Institute, Department of Medical Biophysics and Immunology, University of Toronto, Toronto, Ontario M4X 1K9, Canada
3 Department of Immunology, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812, Japan

Correspondence to: S. Habu

The differentiation process from CD4CD8 double-negative (DN) thymocytes to CD4+CD8+ double-positive (DP) stage is accompanied by vigorous proliferation. The resulting DP cells contain a sizable proportion of large cycling cells, but most DP cells are small resting cells. To explore the molecular mechanisms which regulate cell proliferation of DP thymocytes prior to further development, we used TCR-transgenic (Tg) mice with non-selecting MHC (Tg-Neut), which contain almost exclusively DP thymocytes that are not subject to either positive or negative selection. In Tg-Neut, the thymus contained DP cells of relatively large size, which showed higher extracellular signal-regulated kinase activity and enhanced responsiveness to mitogen compared to small DP cells. This indicates that all the large DP cells in the thymus are not positively selected and that they possess proliferative potential. When Tg-Neut mice were backcrossed with CD45 knockout mice (CD45–/– Tg-Neut), the thymus showed an increase of large DP cells and cycling cells, but a decrease of apoptotic cells. Furthermore, Bcl-2 expression and Jun N-terminal kinase activity, which are associated with resistance to apoptosis, were enhanced. These observations suggest that thymocyte proliferation in the DP stage is suppressed by a CD45-related process with regulation of mitogen-activated protein kinase and Bcl-2 unless DP cells receive TCR-mediated signals.

Keywords: apoptosis, cellular proliferation, thymus

Transmitting editor: T. Watanabe


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S. Nunomura, T. Sato, and S. Habu
Molecular Basis for Functional Maturation of Thymocytes: Increase in c-fos Translation with Positive Selection
J. Immunol., June 1, 2000; 164(11): 5590 - 5595.
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