The influence of thymic abnormalities on the development of autoimmune diseases

The relationship between thymic abnormalities and development of autoimmune diseases was studied in MRL/l and NZB/NZW F1 (NZB/W F1) mice. Thymic abnormalities, including plasma cell infiltration into the thymus, were observed in 25% of MRL/l mice as early as 1 mo and in all mice after 2.5 mo. The thymic abnormalities preceded both infiltration of lymphoid cells into the kidney and salivary glands, and also preceded an increase in the titer of circulating immune complexes (CIC). When MRL/l and NZB/W F1 mice were divided into two groups for each strain at the critical age when the mice had begun to show thymic abnormalities, the group with abnormal thymuses showed more marked pathological findings in other organs and a higher level of CIC than the group with more normal appearing thymus. In addition, the group with abnormal thymus demonstrated lower responsiveness of their lymphocytes in mixed-lymphocyte culture than the group with normal thymus. Thymus grafts from donors of autoimmune or non-autoimmune strains into nude mice revealed that thymic functions, reconstitutive of immunologic parameters of nude mice, are rapidly lost with age. These results suggest that morphological and functional abnormalities of the thymus are involved in the pathogenesis of autoimmune diseases.