EVIDENCE FOR POLYCLONAL T-CELL ACTIVATION IN MURINE MODELS OF SYSTEMIC LUPUS-ERYTHEMATOSUS

CD4(+) T cells have been shown to be important in the development of d isease in murine models of SLE, We compared the TCR V beta repertoires of young (healthy) and older (diseased) New Zealand hybrid mice as we ll as non-autoimmune strains to characterize changes in TCR usage asso ciated with the development of disease. Despite large increases in the total number of splenic CD4(+) T cells with age in diseased mice, we noted little skewing of the V beta repertoire. For example, diseased N ZB.H2(bm12) mice failed to exhibit a significant change in the percent age of any V beta subset despite a fivefold increase in the number of CD4(+) T cells. Strains without lupus-like disease, including NZB.H-2( b) mice, demonstrated no increase in CD4(+) T cell numbers with age. S imilar to NZB. H-2(bm12) mice, (NZB x SWR)F-1 and (NZB x NZW)F-1 mice showed disease-related increases in CD4(+) T cell numbers, but no chan ges in V beta repertoire that could be linked to disease development. Differences in V beta usage between young autoimmune and non-autoimmun e strains of mice matched for either MHC or background genes were cons istent with genetic influences unrelated to disease. Overall, the hete rogeneous repertoire of proliferating T cells provides evidence for po lyclonal T cell expansion in murine models of lupus and suggests that activation either involves a multitude of conventional self-antigens o r may be independent of the TCR. However, the requirement for specific class II MHC molecules suggests that this polyclonal T cell expansion is dependent on a much smaller and specific autoreactive response.