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

• Published in: The Journal of immunology (1950) 2000-12, Vol.165 (12), p.7270-7277
• Main Authors: Paul, A G, van Kooten, P J, van Eden, W, van der Zee, R
• Format: Article
• Language: English
• Subjects: 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; Hsp60 protein; 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
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.165.12.7270

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.