Pathogenesis of autoimmunity in αβ T cell-deficient lupus-prone mice

S. L. Peng, J. Cappadona, J. M. Mcniff, M. P. Madaio, M. J. Owen, A. C. Hayday, J. Craft

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31 Scopus citations

Abstract

Murine lupus in MRL mice has been strongly attributed to αβ T cell- dependent mechanisms. Non-αβ T cell-dependent mechanisms, such as γδ T cells, have been shown to drive antibody and autoantibody production, but they have not been considered capable of inducing end-organ disease. Here, we have expanded upon the findings of such previous work by examining the mechanism and extent of end-organ disease attainable via γδ T cells and/or non-αβ T cell-dependent mechanisms, assessing two prototypical lupus lesions, renal and skin disease, in TCR α -/- MRL mice that possessed either functional or defective Fas antigen (Fas + or lpr). Observed to 1 year of age, TCR α -/- MRL mice developed disease characterized by increased mortality, overt renal disease and skin lesions. While delayed in onset and/or reduced in severity compared with TCR α +/+ MRL/lpr animals, renal and skin lesions in αβ T cell-deficient animals were clearly increased in severity compared with age-matched control non-autoimmune mice. In contrast to TCR α +/+ MRL mice, whose disease reflected pan-isotype immune complex deposition with significant complement fixation, renal disease in TCR α -/- MRL animals reflected predominantly IgG1 immune complex deposition, with poor complement fixation. Thus, this study demonstrates conclusively that non-αβ T cell-dependent mechanisms can induce renal and skin injury in murine lupus, but at least in the kidney, only via humoral autoimmunity of a relatively non-pathological isotype which results in the delayed onset of end-organ damage.

Original languageEnglish (US)
Pages (from-to)107-116
Number of pages10
JournalClinical and Experimental Immunology
Volume111
Issue number1
DOIs
StatePublished - Jan 1 1998

Keywords

  • Aumoantibodies
  • Autoimmunity
  • Mice
  • Nephritis
  • Skin
  • T lymphocytes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Peng, S. L., Cappadona, J., Mcniff, J. M., Madaio, M. P., Owen, M. J., Hayday, A. C., & Craft, J. (1998). Pathogenesis of autoimmunity in αβ T cell-deficient lupus-prone mice. Clinical and Experimental Immunology, 111(1), 107-116. https://doi.org/10.1046/j.1365-2249.1998.00424.x