HSP60 as a target of anti-ergotypic regulatory T cells.
The 60 kDa heat shock protein (HSP60) has been reported to influence T-cell responses in two ways: as a ligand of toll-like receptor 2 signalling and as an antigen. Here we describe a new mechanism of T-cell immuno-regulation focused on HSP60: HSP60 is up-regulated and presented by activated T cells (HSP60 is an ergotope) to regulatory (anti-ergotypic) T cells. Presentation of HSP60 by activated T cells was found to be MHC-restricted and dependent on accessory molecules - CD28, CD80 and CD86. Anti-ergotypic T cells responded to T-cell HSP60 by proliferation and secreted IFNgamma and TGFbeta1. In vitro, the anti-ergotypic T cells inhibited IFNgamma production by their activated T-cell targets. In vivo, adoptive transfer of an anti-ergotypic HSP60-specific T-cell line led to decreased secretion of IFNgamma by arthritogenic T cells and ameliorated adjuvant arthritis (AA). Thus, the presentation of HSP60 by activated T cells turns them into targets for anti-ergotypic regulatory T cells specific for HSP60. However, the direct interaction between the anti-ergotypic T regulators (anti-HSP60) and the activated T cells also down-regulated the regulators. Thus, by functioning as an ergotope, HSP60 can control both the effector T cells and the regulatory HSP60-specific T cells that control them.
Quintana
Francisco J
FJ
Department of Immunology, The Weizmann Institute of Science, Rehovot, Israel. fquintana@rics.bwh.harvard.edu
Mimran
Avishai
A
Carmi
Pnina
P
Mor
Felix
F
Cohen
Irun R
IR
D000818:Animals; D001324:Autoantigens / Q000276:immunology; D001327:Autoimmune Diseases / Q000276:immunology; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D018834:Chaperonin 60 / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism / Q000502:physiology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D005260:Female; D007111:Immunity, Cellular / Q000187:drug effects; D007249:Inflammation / Q000276:immunology; D007371:Interferon-gamma / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D010446:Peptide Fragments / Q000276:immunology / Q000494:pharmacology; D051381:Rats; D011917:Rats, Inbred Lew; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism; D019444:Vaccines, DNA / Q000494:pharmacology
D001324:Autoantigens; D018834:Chaperonin 60; D018984:Epitopes, T-Lymphocyte; D010446:Peptide Fragments; D019444:Vaccines, DNA; D007371:Interferon-gamma