title: Altered expression level of a systemic nuclear autoantigen determines the fate of immune response to self.
abstract: One of the hallmarks of systemic autoimmune diseases is immune responses to systemic nuclear autoantigens. We have examined the fate of the immune response against a nuclear autoantigen using human U1 small nuclear ribonucleoprotein-A protein (HuA) transgenic (Tg) mice by adoptive transfer of autoreactive lymphocytes. We obtained two Tg lines that have different expression levels of the transgene. After spleen cells from HuA-immunized wild-type mice were transferred to Tg mice and their non-Tg littermates, these recipients were injected with HuA/IFA to induce a recall memory response. HAB69, which expressed a lower amount of HuA, exhibited a vigorous increase in the autoantibody level and glomerulonephritis. Moreover, the autoreactivity spread to 70K autoantigen. Alternatively, in HAB64, which expressed a higher amount of HuA, the production of autoantibody was markedly suppressed. The immune response to HuA autoantigen was impaired as demonstrated in a both delayed-type hypersensitivity response and proliferation assay. This inhibition was Ag-specific and was mediated by T cells. These data suggest that the expression level of systemic autoantigens influences the outcome of the immune response to self.
authors.affiliation: Department of Allergy and Rheumatology, University of Tokyo Graduate School of Medicine, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Kawahata
authors.forename: Y
authors.initials: Y
authors.lastname: Misaki
authors.forename: Y
authors.initials: Y
authors.lastname: Komagata
authors.forename: K
authors.initials: K
authors.lastname: Setoguchi
authors.forename: S
authors.initials: S
authors.lastname: Tsunekawa
authors.forename: Y
authors.initials: Y
authors.lastname: Yoshikawa
authors.forename: J
authors.initials: J
authors.lastname: Miyazaki
authors.forename: K
authors.initials: K
authors.lastname: Yamamoto
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D001323:Autoantibodies / Q000096:biosynthesis*; D001324:Autoantigens / Q000096:biosynthesis* / Q000235:genetics; D002467:Cell Nucleus / Q000235:genetics / Q000276:immunology*; D003433:Crosses, Genetic; D005260:Female; D006801:Humans; D007117:Immunization, Secondary; D008181:Lupus Nephritis / Q000209:etiology / Q000235:genetics / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D016601:RNA-Binding Proteins; D011817:Rabbits; D017412:Ribonucleoprotein, U1 Small Nuclear / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology*; D017634:Self Tolerance / Q000235:genetics; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000637:transplantation; D019076:Transgenes / Q000276:immunology
chemical_list: D001323:Autoantibodies; D001324:Autoantigens; D016601:RNA-Binding Proteins; D017412:Ribonucleoprotein, U1 Small Nuclear; C075339:U1A protein