Th1 Biased Progressive Autoimmunity in Aged Aire- Deficient Mice Accelerated Thymic Epithelial Cell Senescence

Although autoimmune diseases, such as rheumatoid arthritis and systemic lupus erythematosus, are frequently associated with premature aging of the thymus, a direct link is missing between autoimmunity and thymic atrophy. Here we monitored the progression of thymic involution in deficient mice, in which defective negative selection causes spontaneous and progressive development of autoimmunity. In young and middle-aged mice, deficiency appeared to be protective as supported by the reduced β-gal epithelial cells and the enhanced thymic output. However, once the autoimmune phenotype was fully developed in aged deficient mice, their thymuses underwent accelerated involution. In comparison to the age-matched wildtype littermates, old deficient mice showed lower numbers of total thymocytes and recent thymic emigrants but more β-gal thymic epithelial cells. This phenomenon may partly be attributable to the increased number of activated Th1 cells homing to the thymus. This speculation was further supported by the enhanced thymic aging following repeated challenges with complete Freund's adjuvant immunization. Taken together, the present study highlights a unique mechanism by which autoimmunity facilitates the senescence of thymic epithelial cells through returning Th1 cells.