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.