Thymic Influences on Autoimmunity in MRL‐1pr Mice

We have examined the role of the thymus in the development of autoimmunity in MRL/Mp‐lpr/lpr (MRL‐lpr) mice. MRL‐lpr mice develop a lymphoproliferative disorder characterized by features of systemic lupus erythematosus and by massive proliferation of a subpopulation of Lyt‐1+23‐ T cells. Using fluorescein‐conjugated monoclonal antibodies and the fluorescence‐activated cell sorter, we have found an abnormal pattern of differentiation within the MRL‐lpr thymus characterized by a loss of Lyt‐123+ thymocytes and an increased frequency of Lyt‐1+23‐ thymocytes. Neonatal thymectomy retarded lymphoproliferation, reduced autoantibody concentrations, improved renal function, and prolonged life. Furthermore, neonatal thymectomy resulted in a relatively specific elimination of the subset of T cells involved in the lymphoproliferative process. These findings suggest that thymic maturation of T cells with alloantigenic characteristics of a helper subpopulation may contribute to the marked lymphoproliferation and severe autoimmunity of MRL‐lpr mice. Neonatal thymectomy may protect against autoimmunity by preventing the maturation of this helper subpopulation.