T cells reactive to an inducible heat shock protein induce disease in toxin-induced interstitial nephritis

Roberta A. Weiss, Michael P. Madaio, John E. Tomaszewski, Carolyn J. Kelly

Research output: Contribution to journalArticle

48 Scopus citations

Abstract

T cells reactive against immunodominant regions of inducible heat shock proteins (HSPs) have been identified in the chronic inflammatory lesions of several experimental autoimmune diseases. Since HSPs are known to be induced by a number of renal tubular epithelial cell toxins associated with chronic interstitial nephritis, we investigated the relevance of HSP expression and T cell reactivity to HSP70 in a model of progressive inflammatory interstitial nephritis. Chronic administration of cadmium chloride (CdClz) to SJL/J mice induces HSP70 expression in renal tubular cells 4-5 wk before the development of interstitial mononuclear cell infiltrates. CdC12 also induces HSP70 expression in cultured tubular epithelial cells from SJL/J mice. CD4+, TCR-α/β+T cell lines specific for an immunodominant HSP peptide are cytotoxic to heat stressed or CdClz-treated renal tubular cells. Such HSP-reactive T cells mediate an inflammatory interstitial nephritis after adoptive transfer to CdClz-treated mice at a time when immunoreactive HSPT0 is detectable in the kidneys, but before the development of interstitial mononuclear cell infiltrates. T cells isolated from the nephritic kidneys of mice treated with CdC12 for 13 wk are also cytotoxic to heat shocked or cadmium-treated tubular cells. These kidney-derived T cells additionally induced interstitial nephritis after passive transfer, indicating their pathogenic significance. Our studies strongly support a role for HSP-reactive T ceils in CdC12-induced interstitial nephritis and suggest that the induction of HSPs in the kidney by a multitude of "nonimmune" events may initiate or facilitate inflammatory damage by HSP-reactive lymphocytes.

Original languageEnglish (US)
Pages (from-to)2239-2250
Number of pages12
JournalJournal of Experimental Medicine
Volume180
Issue number6
DOIs
StatePublished - Dec 1 1994

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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