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 res ponse against a nuclear autoantigen using human U1 small nuclear ribonucleo protein-A protein (HuA) transgenic (Tg) mice by adoptive transfer of autore active lymphocytes, We obtained two Tg lines that have different expression levels of the transgene. After spleen cells from HuA-inmunized wild-type m ice. were transferred to Tg mice and their non-Tg littermates, these recipi ents 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 sp read 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 d elayed-type hypersensitivity response and proliferation assay. This inhibit ion was Ag-specific and was mediated by T cells. These data suggest that th e expression level of systemic autoantigens influences the outcome of the i mmune response to self.