Disparate T cell requirements of two subsets of lupus-specific autoantibodies in pristane-treated mice

Clin Exp Immunol. 1999 Mar;115(3):547-53. doi: 10.1046/j.1365-2249.1999.00825.x.

Abstract

Intraperitoneal injection of pristane induces a lupus-like disease in BALB/c and other non-autoimmune mice characterized by autoantibody production and the development of immune complex disease closely resembling lupus nephritis. Two subsets of autoantibodies are induced by pristane: IgG anti-DNA DNA and -chromatin autoantibodies are strongly IL-6-dependent, whereas IgG anti-nRNP/Sm and -Su antibodies are not. The present studies were carried out to examine the role of T cells in establishing this dichotomy between the production of anti-nRNP/Sm/Su versus anti-DNA/chromatin autoantibodies. Autoantibody production and renal disease were evaluated in athymic (nude) mice treated with pristane. BALB/c nu/nu mice spontaneously developed IgM and IgG anti-single-stranded (ss)DNA and -chromatin, but not anti-nRNP/Sm or -Su, autoantibodies. Pristane treatment increased the levels of IgG anti-chromatin antibodies in nu/nu mice, but did not induce production of anti-nRNP/Sm or -Su antibodies. In contrast, BALB/c nu/+ and +/+ control mice did not spontaneously produce autoantibodies, whereas anti-nRNP/Sm and -Su autoantibodies were induced by pristane in approx. 50% of nu/+ and +/+ mice and anti-DNA/chromatin antibodies at lower frequencies. Nude mice spontaneously developed mild renal lesions that were marginally affected by pristane, but were generally milder than the lesions developing in pristane-treated nu/+ and +/+ mice. The data provide further evidence that two distinct pathways with different cytokine and T cell requirements are involved in autoantibody formation in pristane-induced lupus. This dichotomy may be relevant to understanding differences in the regulation of anti-DNA versus anti-nRNP/Sm autoantibodies in systemic lupus erythematosus, as well as the association of anti-DNA, but not anti-nRNP/Sm, with lupus nephritis.

Publication types

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

MeSH terms

  • Animals
  • Antibodies, Antinuclear / biosynthesis
  • Autoantibodies / biosynthesis*
  • Autoantibodies / classification*
  • Autoantigens
  • Chromatin / immunology
  • DNA, Single-Stranded / immunology
  • Female
  • Glomerulonephritis / chemically induced
  • Glomerulonephritis / immunology
  • Glomerulonephritis / pathology
  • Immune Complex Diseases / chemically induced
  • Immune Complex Diseases / immunology
  • Immune Complex Diseases / pathology
  • Lupus Erythematosus, Systemic / chemically induced
  • Lupus Erythematosus, Systemic / immunology*
  • Lupus Erythematosus, Systemic / pathology
  • Lupus Nephritis / chemically induced
  • Lupus Nephritis / immunology
  • Lupus Nephritis / pathology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Proteins / immunology
  • Ribonucleoproteins / immunology
  • Ribonucleoproteins, Small Nuclear*
  • T-Lymphocytes / immunology*
  • Terpenes / toxicity
  • snRNP Core Proteins

Substances

  • Antibodies, Antinuclear
  • Autoantibodies
  • Autoantigens
  • Chromatin
  • DNA, Single-Stranded
  • Proteins
  • Ribonucleoproteins
  • Ribonucleoproteins, Small Nuclear
  • Su autoantigen
  • Terpenes
  • snRNP Core Proteins
  • pristane