Thymic influences on autoimmunity in MRL-lpr 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.
D000818:Animals; D000831:Animals, Newborn; D001323:Autoantibodies / Q000096:biosynthesis; D001327:Autoimmune Diseases / Q000276:immunology* / Q000401:mortality / Q000628:therapy; D001806:Blood Urea Nitrogen; D004247:DNA / Q000276:immunology; D005260:Female; D008206:Lymphatic Diseases / Q000175:diagnosis / Q000276:immunology; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains / Q000276:immunology*; D011507:Proteinuria / Q000175:diagnosis; D013601:T-Lymphocytes / Q000145:classification / Q000276:immunology; D013934:Thymectomy; D013950:Thymus Gland / Q000276:immunology*
D001323:Autoantibodies; D004247:DNA