INDUCTION OF NONPATHOLOGIC, HUMORAL AUTOIMMUNITY IN LUPUS-PRONE MICE BY A CLASS II-RESTRICTED, TRANSGENIC ALPHA-BETA-T-CELL - SEPARATION OFAUTOANTIGEN-SPECIFIC AND AUTOANTIGEN-NONSPECIFIC HELP

Murine lupus predominantly requires alpha beta T cells, which provide pathogenic help for autoantibody production and immune complex-associa ted end-organ disease. Autoantigen-specific, pathogenic alpha beta T c ells have been isolated from some lupus-prone mice, but a requirement for such T cells in disease has not been clearly demonstrated. To addr ess alpha beta T cell specificity in murine lupus, lupus-prone mice we re generated that contained only a single population of alpha beta T c ells of foreign specificity by generating anti-pigeon cytochrome c (AN D) TCR transgenic TCR alpha -/- TCR beta -/- MRL/Mp-Ipr/Ipr (MRL/Ipr) mice, which lacked the ability to express endogenous TCR alpha or -bet a genes. These AND alpha beta T cells induced hypergammaglobulinemia a nd autoantibody production, as seen in serum Ig, anti-DNA, anti-small nuclear ribonucleoprotein (snRNP) and rheumatoid factor titers, but fa iled to promote the development of lymphadenopathy or pathogenic immun e-complex disease, as assayed by cutaneous, renal, and salivary gland lesions. Thus, antigen-nonspecific alpha beta T cell help can promote generalized autoimmunity, but autoantigen-specific cup T cells are req uired to cause overt disease.