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International Immunology Advance Access originally published online on June 10, 2004
International Immunology 2004 16(7):1027-1035; doi:10.1093/intimm/dxh104
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International Immunology, Vol. 16, No. 7, pp. 1027-1035, July 2004
© 2004 Japanese Society for Immunology

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

Nobuyuki Yajima, Kazuhiro Sakamaki and Shin Yonehara

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

Correspondence to: S. Yonehara; E-mail: syonehar{at}virus.kyoto-u.ac.jp
Transmitting editor: S. Nagata

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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