Altered expression level of a systemic nuclear autoantigen determines the fate of immune response to self.
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.
Kawahata
K
K
Department of Allergy and Rheumatology, University of Tokyo Graduate School of Medicine, Japan.
Misaki
Y
Y
Komagata
Y
Y
Setoguchi
K
K
Tsunekawa
S
S
Yoshikawa
Y
Y
Miyazaki
J
J
Yamamoto
K
K
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
D001323:Autoantibodies; D001324:Autoantigens; D016601:RNA-Binding Proteins; D017412:Ribonucleoprotein, U1 Small Nuclear; C075339:U1A protein