Antigen-specific therapy of murine lupus nephritis using nucleosomal peptides: Tolerance spreading impairs pathogenic function of autoimmune T and B cells

Arunan Kaliyaperumal, Marissa A. Michaels, Syamal K. Datta*

*Corresponding author for this work

Research output: Contribution to journalArticle

137 Scopus citations

Abstract

In the (SWR x NZB)F1 mouse model of lupus, we previously localized the critical autoepitopes for nephritogenic autoantibody-inducing Th cells in the core histones of nucleosomes at aa positions 10-33 of H2B and 16-39 and 71- 94 of H4. A brief therapy with the peptides administered i.v. to 3-mo-old prenephritic (SWR x NZB)F1 mice that were already producing pathogenic autoantibodies markedly delayed the onset of severe lupus nephritis. Strikingly, chronic therapy with the peptides injected into 18-mo-old (SWR x NZB)F1 mice with established glomerulonephritis prolonged survival and even halted the progression of renal disease. Remarkably, tolerization with any one of the nucleosomal peptides impaired autoimmune T cell help, inhibiting the production of multiple pathogenic autoantibodies. However, cytokine production or proliferative responses to the peptides were not grossly changed by the therapy. Moreover, suppressor T cells were not detected in the treated mice. Most interestingly, the best therapeutic effect was obtained with nucleosomal peptide H416-39, which had a tolerogenic effect not only on autoimmune Th cells, but autoimmune B cells as well, because this peptide contained both T and B cell autoepitopes. These studies show that the pathogenic T and B cells of lupus, despite intrinsic defects in activation thresholds, are still susceptible to autoantigen-specific tolerogens.

Original languageEnglish (US)
Pages (from-to)5775-5783
Number of pages9
JournalJournal of Immunology
Volume162
Issue number10
StatePublished - May 15 1999

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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