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Department of Immunology, Weizmann Institute of Science, Rehovot, Israel
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-
secretion to HSP60 and,
concomitantly, to down-regulation of IFN- 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 TGF
1 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.
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