Age-related thymic involution is mediated by Fas on thymic epithelial cells.
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.
Yajima
Nobuyuki
N
Graduate School of Biostudies and Institute for Virus Research, Kyoto University, Sakyo-ku, Kyoto 606-8507, Japan.
Sakamaki
Kazuhiro
K
Yonehara
Shin
S
D000375:Aging / Q000235:genetics / Q000276:immunology*; D000818:Animals; D016026:Bone Marrow Transplantation; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D004847:Epithelial Cells / Q000166:cytology / Q000276:immunology*; D005720:Gamma Rays; D051379:Mice; D018345:Mice, Knockout; D018124:Receptors, Tumor Necrosis Factor / Q000172:deficiency* / Q000235:genetics / Q000276:immunology*; D013950:Thymus Gland / Q000166:cytology / Q000254:growth & development / Q000276:immunology*; D019014:fas Receptor
C491899:Fas protein, mouse; D018124:Receptors, Tumor Necrosis Factor; D019014:fas Receptor