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 ha s been shown to protect rats from experimental arthritis. Previously, the p rotection-inducing capacity was shown to reside in the evolutionary conserv ed parts of the molecule. Now we have studied the nature of the arthritis s uppressive capacity of a distinct, antigenically unrelated protein, M, tube rculosis hsp70, Again, a conserved mycobacterial hsp70 sequence was found t o be immunogenic and to induce T cells that cross-reacted with the rat homo logue sequence. However, in this case parenteral immunization with the pept ide containing the critical crossreactive T cell epitope did not suppress d isease. Upon analysis of cytokines produced by these peptide-specific T cel ls, high IL-10 production was found, as was the case with T cells responsiv e to whole hsp70 protein. Nasal administration of this peptide was found to lead to inhibition of subsequent adjuvant arthritis induction. The data pr esented here shows the intrinsic capacity of conserved bacterial hsp to tri gger self-hsp cross-reactive T cells with the potential to down-regulate ar thritis via IL-10.