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

H. B. Richards, M. Satoh, J. C. Jennette, T. Okano, Y. S. Kanwar, Westley H. Reeves*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

28 Scopus citations

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 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.

Original languageEnglish (US)
Pages (from-to)547-553
Number of pages7
JournalClinical and Experimental Immunology
Volume115
Issue number3
DOIs
StatePublished - 1999

Keywords

  • Autoantibodies
  • Autoimmunity
  • Mouse models
  • Pristane
  • Systemic lupus erythematosus

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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