Evidence for polyclonal T cell activation in murine models of systemic lupus erythematosus

Stephen J. Rozzo, Charles G. Drake, Bor Luen Chiang, M. Eric Gershwin, Brian L. Kotzin

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Abstract

CD4+ T cells have been shown to be important in the development of disease in murine models of SLE. We compared the TCR Vβ 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 Vβ repertoire. For example, diseased NZB.H-2(bm12) mice failed to exhibit a significant change in the percentage of any Vβ 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-2(bm12) mice, (NZB x SWR)F1 and (NZB x NZW)F1 mice showed disease-related increases in CD4+ T cell numbers, but no changes in Vβ repertoire that could be linked to disease development. Differences in Vβ 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.

Original languageEnglish (US)
Pages (from-to)1340-1351
Number of pages12
JournalJournal of Immunology
Volume153
Issue number3
StatePublished - Aug 1 1994

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ASJC Scopus subject areas

  • Immunology

Cite this

Rozzo, S. J., Drake, C. G., Chiang, B. L., Gershwin, M. E., & Kotzin, B. L. (1994). Evidence for polyclonal T cell activation in murine models of systemic lupus erythematosus. Journal of Immunology, 153(3), 1340-1351.