Greatly accelerated lymphadenopathy and autoimmune disease in lpr mice lacking tumor necrosis factor receptor I

J Immunol. 1996 Apr 15;156(8):2661-5.

Abstract

Fas and TNF receptor I (TNF-RI) share homology at their cytoplasmic death domain and belong to the same gene family, but utilize different pathways to signal activation-induced cell death. To determine the combined effects of defective TNF-RI and Fas signaling on lymphadenopathy and autoimmune disease, we backcrossed TNF-RI knockout mice (Tnfr1(0/0)) with Fas-deficient C57BL/6-lpr/lpr mice. Tnfr1(0/0)lpr/lpr mice developed greatly accelerated lymphadenopathy and autoantibody production compared with C57BL/6-lpr/ lpr mice. Tnfr1(0/0)-lpr/lpr mice also exhibited high mortality and early onset autoimmune disease characterized by massive mononuclear cell infiltration in liver, kidney, lung, and knee joints. These results indicate that the Fas-mediated apoptosis defect in lpr mice is accelerated in the absence of TNF-RI and that normal expression of TNF-RI might partially compensate for the Fas-mediated apoptosis defect of mononuclear cells in lpr mice.

Publication types

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

MeSH terms

  • Animals
  • Autoantibodies / biosynthesis
  • Autoimmune Diseases / genetics*
  • Autoimmune Diseases / mortality
  • Autoimmune Diseases / pathology*
  • Cell Movement / genetics
  • Cell Movement / immunology
  • Female
  • Immunoglobulin G / biosynthesis
  • Lymph Nodes / pathology*
  • Lymphatic Diseases / genetics*
  • Lymphatic Diseases / mortality
  • Lymphatic Diseases / pathology*
  • Lymphocyte Activation / genetics*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Receptors, Tumor Necrosis Factor / deficiency*
  • Receptors, Tumor Necrosis Factor / genetics*

Substances

  • Autoantibodies
  • Immunoglobulin G
  • Receptors, Tumor Necrosis Factor