hsp60 as a target of anti-ergotypic regulatory t cellshsp60 anti-ergotypic调节性t细胞的一个目标.pdfVIP

HSP60 as a Target of Anti-Ergotypic Regulatory T Cells 1,2 2 2 2 2 Francisco J. Quintana *, Avishai Mimran , Pnina Carmi , Felix Mor , Irun R. Cohen 1 Department of Immunology, The Weizmann Institute of Science, Rehovot, Israel, 2 Center for Neurologic Diseases, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, United States of America Abstract 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 IFNc and TGFb1. In vitro, the anti-ergotypic T cells inhibited IFNc 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 IFNc 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