Aβ t cell-dependent and -independent contributions to autoimmunity in lupus-prone mrump-lpr/lprwce

S. Penget, M. Madaio, S. D. Hughes, N. Crispe, M. Owenï, A. Haydays, J. Craft

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Abstract

MRL/Mp-/pr)rmice develop a spontaneous lupus syndrome, including glomerulonephritis, hypergammaglobulinemia, and lymphadenopathy, as well as the production of anti-double stranded (ds) DNA, anti-small nuclear ribonucleoprotein particles (snRNP), and rheumatoid factor (RF) antibodies. To investigate the role of lymphocyte subsets in the pathogenesis of disease, MRL/lpr mice were made deficient in aβ T cells via the backcrossing of a TCR a -/- mutation. Examined at twelve and eighteen weeks, TCR a -/- MRL/Mp-/pr/îpr mice developed reduced lymphadenopathy, hypergammaglobulinemia, autoantibodies, and glomerulonephritis in comparison to wildtype animals. Still, they still generated a partially penetrant form of lupus, characterized by minimal lymphadenopathy, elevated levels of class-switched immunoglobulins, increased incidences of antinuclear antibodies as assayed by immunofluorescence, and immune deposits in kidneys. While TCR a -/- animals developed grossly reduced levels of rheumatoid factor, they produced anti-snRNP antibodies with frequencies similar to that of controls, as well as as partial autoimmunity to dsDNA, characterized by ELIS Apositive, but Crithidia kinetoplast-negative antibodies. These findings demonstrate that murine lupus in the setting of Fas-deficiency does not absolutely require the presence of aβ T cells. They also suggest that a significant basis for MRLJIpr disease, including renal immune deposits, involves aβ T cell-independent, polyreactive B cell autoimmunity, upon which aβ T cell-dependent mechanisms aggravate specific autoimmune responses.

Original languageEnglish (US)
Pages (from-to)222a
JournalJournal of Investigative Medicine
Volume44
Issue number3
StatePublished - Jan 1 1996

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ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Penget, S., Madaio, M., Hughes, S. D., Crispe, N., Owenï, M., Haydays, A., & Craft, J. (1996). Aβ t cell-dependent and -independent contributions to autoimmunity in lupus-prone mrump-lpr/lprwce. Journal of Investigative Medicine, 44(3), 222a.