Induction of IL-10 and inhibition of experimental arthritis are specific features of microbial heat shock proteins that are absent for other evolutionarily conserved immunodominant proteins

Bacterial heat shock proteins (lisp) are evolutionary conserved immunodomin ant proteins that manifest amino acid homologies with lisp present in mamma lian cells. Preimmunization with mycobacterial hsp65 has been found to prot ect against various forms of experimental arthritis. As these protective ef fects have previously been attributed to induction of self homologue cross- reactive T cell responses, the question was raised as to whether this prote ctive effect could be extended to other highly conserved and immunodominant microbial Ags with mammalian homologues. Therefore, we immunized Lewis rat s with conserved bacterial Ags (superoxide dismutase, aldolase, GAPDH, and hsp70). Although all Ags appeared highly immunogenic, we only found a prote ctive effect in experimental arthritis after immunization with bacterial hs p70. The protective effect of hsp70 was accompanied with a switch in the su bclasses of hsp70-specific Abs, suggesting the induction of Th2-like respon se. The most striking difference between immunization with hsp70 and all ot her immunodominant Ags was the expression of IL-10 found after immunization with hsp70. Even more, while immunization with hsp70 led to Ag-induced pro duction of IL-10 and IL-4, immunization with aldolase led to increased prod uction of IFN-gamma and TNF-alpha. Thus, the protective effect of conserved immunodominant proteins in experimental arthritis seems to be a specific f eature of lisp. Therefore, lisp may offer unique possibilities for immunolo gical intervention in inflammatory diseases.