Highly autoproliferative T cells specific for 60-kDa heat shock protein produce IL-4/IL-10 and IFN-gamma and are protective in adjuvant arthritis

J Immunol. 2000 Dec 15;165(12):7270-7. doi: 10.4049/jimmunol.165.12.7270.

Abstract

Previously we have shown that T cell responses to the mycobacterial 60-kDa heat shock protein (hsp60) peptide M256-270 mediated protection against adjuvant arthritis in Lewis rats. We have demonstrated now that M256-270-primed T cells become highly reactive to naive syngeneic APC upon repetitive restimulation in vitro with peptide M256-265, comprising the conserved core of peptide M256-270. These autoproliferative responses in the absence of added Ag were MHC class II restricted and resulted in the production of IL-4/IL-10 and IFN-gamma. Enhanced autoproliferation and expression of the cell surface molecule B7.2 by these T cells were observed in response to syngeneic heat-shocked APC, which indicated that the autoproliferation and expression of B7.2 resulted from the recognition of endogenously expressed and processed hsp. Despite their strong autoreactivity, upon transfer such T cells were found to induce a significant disease reduction in adjuvant arthritis. In contrast, T cells both primed and restimulated with peptide M256-270 became unresponsive toward syngeneic APC as well as toward the conserved core peptide M256-265, and they were devoid of protective capacity. This study demonstrates that the loss of self-tolerance toward hsp60 does not necessarily lead to autoimmune disease, but that hsp60-specific self-reactive and autoproliferative T cells may mediate T cell regulation in arthritis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antigen-Presenting Cells / immunology
  • Antigen-Presenting Cells / metabolism
  • Antigens, CD / biosynthesis
  • Arthritis, Experimental / immunology
  • Arthritis, Experimental / prevention & control*
  • Autoantigens / immunology
  • B7-2 Antigen
  • Cell Line
  • Chaperonin 60 / immunology*
  • Chaperonin 60 / metabolism
  • Conserved Sequence
  • Epitopes, T-Lymphocyte / immunology*
  • Histocompatibility Antigens / genetics
  • Histocompatibility Antigens / immunology
  • Injections, Intravenous
  • Interferon-gamma / biosynthesis*
  • Interleukin-10 / biosynthesis*
  • Interleukin-4 / biosynthesis*
  • Lymphocyte Activation*
  • Male
  • Membrane Glycoproteins / biosynthesis
  • Molecular Sequence Data
  • Peptide Fragments / immunology
  • Rats
  • Rats, Inbred F344
  • Rats, Inbred Lew
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocyte Subsets / metabolism
  • T-Lymphocyte Subsets / transplantation

Substances

  • Antigens, CD
  • Autoantigens
  • B7-2 Antigen
  • Cd86 protein, rat
  • Chaperonin 60
  • Epitopes, T-Lymphocyte
  • Histocompatibility Antigens
  • Membrane Glycoproteins
  • Peptide Fragments
  • histocompatibility antigens RT, rat
  • Interleukin-10
  • Interleukin-4
  • Interferon-gamma