Abstract
Adjuvant arthritis (AA) is induced using Mycobacterium tuberculosis (Mt). Immunization with mycobacterial heat shock proteins (HSPs) inhibits AA, supposedly by the induction of T cell responses cross-reactive with self-HSPs. Indeed, vaccination with the human 60-kDa HSP (HSP60) inhibits AA. In this work we studied the control of AA by self-HSP molecules other than HSP60 using DNA vaccines coding for the human 70 kDa (pHSP70) or 90 kDa (pHSP90) HSPs. pHSP70 and pHSP90 down-regulated the arthritogenic T-cell response and inhibited AA. In addition, both pHSP70 and pHSP90 induced T-cell responses to HSP60, and vaccination with pHSP70 triggered the release of endogenous HSP60 to the circulation. Thus the regulatory activities of HSP on inflammation might involve two types of cross-reactivity: molecular cross-reactivity exists between microbial and self-HSPs, and network cross-reactivity exists between different self-HSPs.