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 language||English (US)|
|Journal||Journal of Investigative Medicine|
|State||Published - Jan 1 1996|
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)