title: 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.
abstract: Bacterial heat shock proteins (hsp) are evolutionary conserved immunodominant proteins that manifest amino acid homologies with hsp present in mammalian cells. Preimmunization with mycobacterial hsp65 has been found to protect against various forms of experimental arthritis. As these protective effects have previously been attributed to induction of self homologue cross-reactive T cell responses, the question was raised as to whether this protective effect could be extended to other highly conserved and immunodominant microbial Ags with mammalian homologues. Therefore, we immunized Lewis rats with conserved bacterial Ags (superoxide dismutase, aldolase, GAPDH, and hsp70). Although all Ags appeared highly immunogenic, we only found a protective effect in experimental arthritis after immunization with bacterial hsp70. The protective effect of hsp70 was accompanied with a switch in the subclasses of hsp70-specific Abs, suggesting the induction of Th2-like response. The most striking difference between immunization with hsp70 and all other immunodominant Ags was the expression of IL-10 found after immunization with hsp70. Even more, while immunization with hsp70 led to Ag-induced production of IL-10 and IL-4, immunization with aldolase led to increased production of IFN-gamma and TNF-alpha. Thus, the protective effect of conserved immunodominant proteins in experimental arthritis seems to be a specific feature of hsp. Therefore, hsp may offer unique possibilities for immunological intervention in inflammatory diseases.
authors.affiliation: Institute of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht, The Netherlands.
authors.forename: B J
authors.initials: BJ
authors.lastname: Prakken
authors.forename: U
authors.initials: U
authors.lastname: Wendling
authors.forename: R
authors.initials: R
authors.lastname: van der Zee
authors.forename: V P
authors.initials: VP
authors.lastname: Rutten
authors.forename: W
authors.initials: W
authors.lastname: Kuis
authors.forename: W
authors.initials: W
authors.lastname: van Eden
mesh_terms: D019264:Adoptive Transfer; D000595:Amino Acid Sequence; D000818:Animals; D000942:Antigens, Bacterial / Q000627:therapeutic use*; D001169:Arthritis, Experimental / Q000517:prevention & control*; D001426:Bacterial Proteins; D018834:Chaperonin 60; D018833:Chaperonins; D017124:Conserved Sequence; D019143:Evolution, Molecular; D005634:Fructose-Bisphosphate Aldolase / Q000276:immunology; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000276:immunology; D018840:HSP70 Heat-Shock Proteins / Q000627:therapeutic use*; D016056:Immunodominant Epitopes / Q000627:therapeutic use*; D016753:Interleukin-10 / Q000096:biosynthesis*; D009161:Mycobacterium / Q000276:immunology; D051381:Rats; D011917:Rats, Inbred Lew; D013482:Superoxide Dismutase / Q000276:immunology
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D018834:Chaperonin 60; D018840:HSP70 Heat-Shock Proteins; D016056:Immunodominant Epitopes; C074119:heat-shock protein 65, Mycobacterium; D016753:Interleukin-10; D013482:Superoxide Dismutase; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases; D018833:Chaperonins; D005634:Fructose-Bisphosphate Aldolase