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Susceptibility to involution of the thymus-dependent lymphoid system and autoimmunity.

Antibodies against cellular antigens appear during aging in some strains of mice but not others. In susceptible strains, manifestations of autoimmunity include development of Coombs positive hemolytic anemia, circulating anti-DNA and anti-desoxynucleoprotein antibodies, positive LE cells, and immunologically based renal and cardiac lesions. Neonatal thymectomy may accelerate development of these autoimmune phenomena. The autoimmune susceptible strains are prone to lose immune capacities (particularly cell-mediated immune responses) with aging. Thymectomy accelerates the development of immune deficiency and autoimmunity. Reconstitution with a sufficient number of postthymic immune competent cells can reverse not only the evidence of immune deficiency, but also wasting and autoimmune phenomena. In some strains not susceptible to development of autoimmunity with aging, there is increased evidence of autoimmunity of lesser degree and frequency than that observed in autoimmune strains after thymectomy. These findings suggest that involution of the thymic system is related to autoimmunity and that genetic factors are involved in the involution of the thymus dependent system. This hypothesis is supported by experiments in which spleen cells from old mice of autoimmune susceptible strains have decreased ability to reconstitute immunologically neonatally thymectomized mice; spleen cells from old mice of autoimmune nonsusceptible strains still can reconstitute neonatally thymectomized mice.