title: Arthritis protective regulatory potential of self-heat shock protein cross-reactive T cells.
abstract: Immunization with heat shock proteins has protective effects in models of induced arthritis. Analysis has shown a reduced synovial inflammation in such protected animals. Adoptive transfer and immunization with selected T cell epitopes (synthetic peptides) have indicated the protection to be mediated by T cells directed to conserved hsp epitopes. This was shown first for mycobacterial hsp60 and later for mycobacterial hsp70. Fine specificity analysis showed that such T cells were cross-reactive with the homologous self hsp. Therefore protection by microbial hsp reactive T cells can be by cross-recognition of self hsp overexpressed in the inflamed tissue. Preimmunization with hsp leads to a relative expansion of such self hsp cross-responsive T cells. The regulatory nature of such T cells may originate from mucosal tolerance maintained by commensal flora derived hsp or from partial activation through recognition of self hsp as a partial agonist (Altered Peptide Ligand) or in the absence of proper costimulation. Recently, we reported the selective upregulation of B7.2 on microbial hsp600 specific T cells in response to self hsp60. Through a preferred interaction with CTLA-4 on proinflammatory T cells this may constitute an effector mechanism of regulation. Also, regulatory T cells produced IL10.
authors.affiliation: Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht, The Netherlands. w.eden@vet.uu.nl
authors.forename: W
authors.initials: W
authors.lastname: van Eden
authors.forename: U
authors.initials: U
authors.lastname: Wendling
authors.forename: L
authors.initials: L
authors.lastname: Paul
authors.forename: B
authors.initials: B
authors.lastname: Prakken
authors.forename: P
authors.initials: P
authors.lastname: van Kooten
authors.forename: R
authors.initials: R
authors.lastname: van der Zee
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D001168:Arthritis / Q000188:drug therapy* / Q000276:immunology*; D003429:Cross Reactions; D006360:Heat-Shock Proteins / Q000276:immunology* / Q000494:pharmacology*; D006801:Humans; D007165:Immunosuppression Therapy; D051381:Rats; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D006360:Heat-Shock Proteins