A conserved mycobacterial heat shock protein (hsp) 70 sequence prevents adjuvant arthritis upon nasal administration and induces IL-10-producing T cells that cross-react with the mammalian self-hsp70 homologue.
Immunization with Mycobacterium tuberculosis heat shock protein (hsp) 60 has been shown to protect rats from experimental arthritis. Previously, the protection-inducing capacity was shown to reside in the evolutionary conserved parts of the molecule. Now we have studied the nature of the arthritis suppressive capacity of a distinct, antigenically unrelated protein, M. tuberculosis hsp70. Again, a conserved mycobacterial hsp70 sequence was found to be immunogenic and to induce T cells that cross-reacted with the rat homologue sequence. However, in this case parenteral immunization with the peptide containing the critical cross-reactive T cell epitope did not suppress disease. Upon analysis of cytokines produced by these peptide-specific T cells, high IL-10 production was found, as was the case with T cells responsive to whole hsp70 protein. Nasal administration of this peptide was found to lead to inhibition of subsequent adjuvant arthritis induction. The data presented here shows the intrinsic capacity of conserved bacterial hsp to trigger self-hsp cross-reactive T cells with the potential to down-regulate arthritis via IL-10.
Wendling
U
U
Institute of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University, The Netherlands.
Paul
L
L
van der Zee
R
R
Prakken
B
B
Singh
M
M
van Eden
W
W
D000280:Administration, Inhalation; D000595:Amino Acid Sequence; D000818:Animals; D001169:Arthritis, Experimental / Q000276:immunology / Q000517:prevention & control*; D001426:Bacterial Proteins / Q000008:administration & dosage / Q000276:immunology; D002460:Cell Line; D017124:Conserved Sequence / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000008:administration & dosage / Q000276:immunology; D018840:HSP70 Heat-Shock Proteins / Q000008:administration & dosage / Q000276:immunology*; D016753:Interleukin-10 / Q000096:biosynthesis*; D008213:Lymphocyte Activation; D008297:Male; D008969:Molecular Sequence Data; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D010446:Peptide Fragments / Q000008:administration & dosage / Q000276:immunology; D051381:Rats; D011917:Rats, Inbred Lew; D017386:Sequence Homology, Amino Acid; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism*
D001426:Bacterial Proteins; D018984:Epitopes, T-Lymphocyte; D018840:HSP70 Heat-Shock Proteins; D010446:Peptide Fragments; D016753:Interleukin-10