Inhibition of Adjuvant Arthritis by a DNA Vaccine Encoding Human Heat Shock Protein 60

Abstract

Adjuvant arthritis (AA) is an autoimmune disease inducible in rats involving T cell reactivity to the mycobacterial 65-kDa heat shock protein (HSP65). HSP65-specific T cells cross-reactive with the mammalian 60-kDa heat shock protein (HSP60) are thought to participate in the modulation of AA. In this work we studied the effects on AA of DNA vaccination using constructs coding for HSP65 (pHSP65) or human HSP60 (pHSP60). We found that both constructs could inhibit AA, but that pHSP60 was more effective than pHSP65. The immune effects associated with specific DNA-induced suppression of AA were complex and included enhanced T cell proliferation to a variety of disease-associated Ags. Effective vaccination with HSP60 or HSP65 DNA led paradoxically to up-regulation of IFN-γ secretion to HSP60 and, concomitantly, to down-regulation of IFN-γ secretion to the P180-188 epitope of HSP65. There were also variable changes in the profiles of IL-10 secretion to different Ags. However, vaccination with pHSP60 or pHSP65 enhanced the production of TGFβ1 to both HSP60 and HSP65 epitopes. Our results support a regulatory role for HSP60 autoreactivity in AA and demonstrate that this control mechanism can be activated by DNA vaccination with both HSP60 or HSP65.

Proteomic analysis in monocytes of antiphospholipid syndrome patients: Deregulation of proteins related to the development of thrombosis

“…Our results are consistent with the significant reduction in Hsp60 levels in PBMCs from rheumatoid arthritis patients (34). Actually, Hsp60 contributes to the suppression of arthritis by stimulating regulatory suppressive T cells (35). On the other hand, although Hsp60 expression increases as a consequence of an inflammatory response, monocyte activation and thrombosis in APS have been proven to not be related to an acute inflammatory response (9).…”

Regulation of autoimmune arthritis by the pro-inflammatory cytokine interferon-γ

“…Arthritic LEW rats raise T cell response to mycobacterial heat shock protein 65 (Bhsp65), and the T cells directed against the determinant region 180-188 and its longer variants are believed to represent the pathogenic subset of T cells [28][29][30][31][32][33]. AA is self-limiting with a gradual regression of inflammation.…”

Protection against renal disease in (NZB × NZW)F1 lupus‐prone mice after somatic B cell gene vaccination with anti‐DNA immunoglobulin consensus peptide

“…Since gene therapy induces antibody to the encoded gene product (13)(14)(15) and since an anti-human IgG response could have influenced the titer of circulating human IgG, we analyzed the serum concentration of anti-human IgG antibody in the different groups of mice. We found similar (low) levels of anti-human IgG antibody in mice that received pIg, pIgCons, and pIgNeg, and the absence of anti-human IgG antibody in control mice that received pCMV and PBS (data not shown).…”