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Molecular Biology Reports

, Volume 23, Issue 3–4, pp 247–251 | Cite as

T cells in murine lupus: propagation and regulation of disease

  • Stanford L. Peng
  • Joe Craft
Features of Autoantigens

Abstract

MRL/Mp-lpr/lpr mice develop a spontaneous lupus syndrome, including hypergammaglobulinemia, autoantibodies, glomerulonephritis, and lymphadenopathy. To investigate the role of lymphocyte subsets in the pathogenesis of disease, lupus-prone MRL mice deficient in αβ T cells, γδ T cells, or both were generated. Mice deficient in αβ T cells developed a partially penetrant lupus syndrome, characterized by lymphadenopathy, elevated levels of class-switched immunoglobulins, an increased incidence of antinuclear antibodies, and immune deposits in kidneys which progressed to renal insufficiency over time. In comparison to wild type animals, γδ T cell-deficient animals developed an accelerated and exacerbated disease phenotype, characterized by accelerated hypergammaglobulinemia and enhanced autoantibody production and mortality. Repertoire analysis of these latter animals identified polyclonal expansion (Vβ) of αβ CD4+B220-cells. Mice lacking both αβ and γδ T cells failed to generate class-switched autoantibodies and immune complex renal disease. First, these findings demonstrate that murine lupus in the setting of Fas-deficiency does not absolutely require the presence of αβ T cells, and they also suggest that a significant basis for MRL/lpr disease, including renal disease, involves αβ T cell-independent, γδ T cell dependent, polyreactive B cell autoimmunity, upon which αβ T cell-dependent mechanisms aggravate specific autoimmune responses. Second, these data indicate that γδ T cells partake in the regulation of systemic autoimmunity, presumably via their effects on αβ CD4+B220-T cells that provide B cell help. Finally, these results demonstrate that MRL/lpr B cells, despite their intrinsic abnormalities, cannot per se cause tissue injury without T cell help.

Key words

animal models autoantibodies autoimmunity lupus B lymphocytes T lymphocytes 

Abbreviations

snRNPs

small nuclear ribonucleoprotein particles

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Copyright information

© Kluwer Academic Publishers 1996

Authors and Affiliations

  • Stanford L. Peng
    • 1
    • 2
  • Joe Craft
    • 1
  1. 1.Section of RheumatologyYale University School of MedicineNew HavenUSA
  2. 2.Department of BiologyYale UniversityUSA

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