Open AccessArthritis protective regulatory potential of self–heat shock protein cross-reactive T cells
Author(s) -
Willem van Eden,
Uwe Wendling,
Alberta G. A. Paul,
Berent J. Prakken,
Peter van Kooten,
Ruurd van der Zee
Publication year - 2000
Publication title -
cell stress and chaperones
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.994
H-Index - 87
eISSN - 1466-1268
pISSN - 1355-8145
DOI - 10.1379/1466-1268(2000)005<0452:aprpos>2.0.co;2
Subject(s) - heat shock protein , epitope , adoptive cell transfer , hsp60 , immunology , proinflammatory cytokine , il 2 receptor , biology , t cell , arthritis , cytotoxic t cell , cross presentation , reactive arthritis , inflammation , microbiology and biotechnology , immune system , hsp70 , antigen presenting cell , antigen , in vitro , biochemistry , gene
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.