Induction of nonpathologic, humoral autoimmunity in lupus-prone mice by a class II-restricted, transgenic alpha beta T cell. Separation of autoantigen-specific and -nonspecific help.
Murine lupus predominantly requires alpha beta T cells, which provide pathogenic help for autoantibody production and immune complex-associated end-organ disease. Autoantigen-specific, pathogenic alpha beta T cells have been isolated from some lupus-prone mice, but a requirement for such T cells in disease has not been clearly demonstrated. To address alpha beta T cell specificity in murine lupus, lupus-prone mice were generated that contained only a single population of alpha beta T cells of foreign specificity by generating anti-pigeon cytochrome c (AND) TCR transgenic TCRalpha -/- TCRbeta -/- MRL/Mp-lpr/lpr (MRL/lpr) mice, which lacked the ability to express endogenous TCRalpha or -beta genes. These AND alpha beta T cells induced hypergammaglobulinemia and autoantibody production, as seen in serum Ig, anti-DNA, anti-small nuclear ribonucleoprotein (snRNP) and rheumatoid factor titers, but failed to promote the development of lymphadenopathy or pathogenic immune-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 alpha beta T cells are required to cause overt disease.
Peng
S L
SL
Department of Biology, Yale University, New Haven, CT 06510, USA.
Fatenejad
S
S
Craft
J
J
D000818:Animals; D001324:Autoantigens / Q000276:immunology*; D015551:Autoimmunity / Q000276:immunology*; D007132:Immunoglobulin Isotypes / Q000096:biosynthesis; D008180:Lupus Erythematosus, Systemic / Q000276:immunology* / Q000473:pathology; D008211:Lymphocyte Cooperation; D051379:Mice; D008822:Mice, Transgenic; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology*
D001324:Autoantigens; D007132:Immunoglobulin Isotypes; D016693:Receptors, Antigen, T-Cell, alpha-beta