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 disease in murine models of SLE. We compared the TCR V beta repertoires of young (healthy) and older (diseased) New Zealand hybrid mice as well as non-autoimmune strains to characterize changes in TCR usage associated 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 NZB.H-2bm12 mice failed to exhibit a significant change in the percentage of any V beta subset despite a fivefold increase in the number of CD4+ T cells. Strains without lupus-like disease, including NZB.H-2b mice, demonstrated no increase in CD4+ T cell numbers with age. Similar to NZB.H-2bm12 mice, (NZB x SWR)F, and (NZB x NZW)F1 mice showed disease-related increases in CD4+ T cell numbers, but no changes in V beta repertoire that could be linked to disease development. Differences in V beta usage between young autoimmune and non-autoimmune strains of mice matched for either MHC or background genes were consistent with genetic influences unrelated to disease. Overall, the heterogeneous repertoire of proliferating T cells provides evidence for polyclonal T cell expansion in murine models of lupus and suggests that activation either involves a multitude of conventional self-antigens or 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.
Rozzo
S J
SJ
Department of Pediatrics, National Jewish Center for Immunology and Respiratory Medicine, Denver, CO 80206.
Drake
C G
CG
Chiang
B L
BL
Gershwin
M E
ME
Kotzin
B L
BL
D000375:Aging; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D016827:CD8 Antigens / Q000032:analysis; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008814:Mice, Inbred NZB; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis; D016176:T-Lymphocyte Subsets / Q000276:immunology*
D016827:CD8 Antigens; D016693:Receptors, Antigen, T-Cell, alpha-beta