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International Immunology Advance Access published online on June 10, 2004
International Immunology, doi:10.1093/intimm/dxh104
© 2004 by The Japanese Society for Immunology
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Received January 7, 2004
Accepted April 26, 2004

Article

Age-related thymic involution is mediated by Fas on thymic epithelial cells

Nobuyuki Yajima 1, Kazuhiro Sakamaki 1, Shin Yonehara 1*

1 Graduate School of Biostudies and Institute for Virus Research, Kyoto University, Sakyo-ku, Kyoto 606-8507, Japan

* To whom correspondence should be addressed. E-mail: syonehar{at}virus.kyoto-u.ac.jp.


  Abstract

Age-related thymic involution, which is linked to senescence of the immune system, was found to be mediated by the death receptor Fas. The thymus of aged Fas-/- mice exhibited an intact structure and the normal differentiation of thymocytes. Both thymocytes and thymic epithelial cells (TECs) were sensitive to Fas-mediated apoptosis, and in vivo stimulation of wild-type thymocytes with anti-CD3 mAb was shown to induce apoptosis in TECs in a Fas-dependent manner. In addition, thymopoiesis continued uninterrupted in aged Fas-/- mice that had been lethally irradiated and reconstituted with bone marrow cells derived from wild-type mice, while age-related thymic involution was observed in irradiated wild-type mice reconstituted with bone marrow cells from either Fas-/- or wild-type mice. The results indicate that Fas on TECs plays a key role in age-related thymic involution.

Keywords: aging, apoptosis, FasL, thymocyte


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