Arthritis protective regulatory potential of self-heat shock protein cross-reactive T cells.
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.
van Eden
W
W
Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht, The Netherlands. w.eden@vet.uu.nl
Wendling
U
U
Paul
L
L
Prakken
B
B
van Kooten
P
P
van der Zee
R
R
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*
D006360:Heat-Shock Proteins