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

Clin Exp Immunol. 1998 Jan;111(1):107-16. doi: 10.1046/j.1365-2249.1998.00424.x.

Abstract

Murine lupus in MRL mice has been strongly attributed to alphabeta T cell-dependent mechanisms. Non-alphabeta T cell-dependent mechanisms, such as gammadelta 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 gammadelta T cells and/or non-alphabeta T cell-dependent mechanisms, assessing two prototypical lupus lesions, renal and skin disease, in TCR alpha -/- MRL mice that possessed either functional or defective Fas antigen (Fas + or lpr). Observed to 1 year of age, TCR alpha -/- 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 alpha +/+ MRL/lpr animals, renal and skin lesions in alphabeta T cell-deficient animals were clearly increased in severity compared with age-matched control non-autoimmune mice. In contrast to TCR alpha +/+ MRL mice, whose disease reflected pan-isotype immune complex deposition with significant complement fixation, renal disease in TCR alpha -/- MRL animals reflected predominantly IgG1 immune complex deposition, with poor complement fixation. Thus, this study demonstrates conclusively that non-alphabeta 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Autoimmunity* / genetics
  • Kidney Diseases / immunology
  • Kidney Diseases / pathology
  • Lupus Vulgaris / genetics
  • Lupus Vulgaris / immunology*
  • Lupus Vulgaris / pathology
  • Mice
  • Receptors, Antigen, T-Cell, alpha-beta / deficiency*
  • Receptors, Antigen, T-Cell, alpha-beta / genetics
  • Receptors, Antigen, T-Cell, alpha-beta / immunology
  • Skin / immunology
  • Skin / pathology
  • T-Lymphocytes / immunology*

Substances

  • Receptors, Antigen, T-Cell, alpha-beta