HSP Reactive T Cells are Anti-Inflammatory and Disease Suppressive in Arthritic Diseases

Abstract

Immune responses to certain heat-shock proteins (HSP) develop in virtually all inflammatory diseases; however, the significance of such responses is only now becoming clear. In models of experimental arthritis, HSPs can prevent or arrest inflammatory damage, and in initial clinical trials in patients with chronic inflammatory diseases, including rheumatoid arthritis, HSP peptides have been shown to promote the production of anti-inflammatory cytokines, indicating immunoregulatory potential of HSP. Heat shock proteins, also called stress-proteins, are ubiquitous self-antigens that are over-expressed in inflamed tissues. For some reason, the prokaryotic homologous proteins, present in every bacterial species, are dominantly immunogenic. This is striking, especially given the fact that these proteins have large areas of sequence homologies with the host (mammalian) counterparts. Furthermore, in experimental models of arthritis, immunisation with bacterial heat shock proteins has been seen to lead to inhibition of disease development. In addition oral or nasal administration has similarly been seen to lead to disease inhibition. Based on the experimental evidence collected, it becomes attractive to suppose that the exposure to homologues of these self antigens, as present in for instance the bacterial intestinal flora, has a decisive impact on the regulation of self tolerance at the level of T cells. If so, it becomes attractive to use such proteins or their derivative peptides for modulation of inflammation relevant T cells as an antigen specific immunotherapy approach, without the immediate necessity of defining disease specific auto-antigens