Disparate T cell requirements of two subsets of lupus-specific autoantibodies in pristane-treated mice

Intraperitoneal injection of pristane induces a lupus-like disease in BALB/ c and other non-autoimmune mice characterized by autoantibody production an d the development of immune complex disease closely resembling lupus nephri tis. Two subsets of autoantibodies are induced by pristane: IgG anti-DNA an d -chromatin autoantibodies are strongly IL-6-dependent, whereas IgG anti-n RNP/Sm and -Su antibodies are not. The present studies were carried out to examine the role of T cells in establishing this dichotomy between the prod uction of anti-nRNP/Sm/Su versus anti-DNA/chromatin autoantibodies. Autoant ibody production and renal disease were evaluated in athymic (nude) mice tr eated with pristane. BALB/c nu/nu mice spontaneously developed IgM and IgG anti-single-stranded (ss) DNA and -chromatin, but not anti-nRNP/Sm or -Su, autoantibodies. Pristane treatment increased the levels of IgG anti-chromat in antibodies in nu/nu mice, but did not induce production of anti-nRNP/Sm or -Su antibodies. In contrast, BALB/c nu/+ and +/+ control mice did not sp ontaneously produce autoantibodies, whereas anti-nRNP/Sm and -Su autoantibo dies were induced by pristane in approx. 50% of nu/+ and +/+ mice and anti- DNA/chromatin antibodies at lower frequencies. Nude mice spontaneously deve loped mild renal lesions that were marginally affected by pristane, but wer e generally milder than the lesions developing in pristane-treated nu/+ and +/+ mice. The data provide further evidence that two distinct pathways wit h different cytokine and T cell requirements are involved in autoantibody f ormation in pristane-induced lupus. This dichotomy may be relevant to under standing differences in the regulation of anti-DNA versus anti-nRNP/Sm auto antibodies in systemic lupus erythematosus, as well as the association of a nti-DNA, but not anti-nRNP/Sm, with lupus nephritis.