Inhibition of adjuvant arthritis by a DNA vaccine encoding human heat shock protein 60.
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-gamma secretion to HSP60 and, concomitantly, to down-regulation of IFN-gamma 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 TGFbeta1 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.
Quintana
Francisco J
FJ
Department of Immunology, Weizmann Institute of Science, Rehovot, Israel.
Carmi
Pnina
P
Mor
Felix
F
Cohen
Irun R
IR
D000276:Adjuvants, Immunologic / Q000138:chemical synthesis / Q000627:therapeutic use; D000818:Animals; D001169:Arthritis, Experimental / Q000276:immunology* / Q000517:prevention & control*; D001426:Bacterial Proteins; D018834:Chaperonin 60 / Q000096:biosynthesis / Q000097:blood / Q000235:genetics* / Q000627:therapeutic use*; D018833:Chaperonins / Q000235:genetics / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007273:Injections, Intramuscular; D007371:Interferon-gamma / Q000037:antagonists & inhibitors / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D008213:Lymphocyte Activation; D009161:Mycobacterium / Q000235:genetics / Q000276:immunology; D051381:Rats; D011917:Rats, Inbred Lew; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism; D015854:Up-Regulation / Q000276:immunology; D019444:Vaccines, DNA / Q000138:chemical synthesis / Q000627:therapeutic use*
D000276:Adjuvants, Immunologic; D001426:Bacterial Proteins; D018834:Chaperonin 60; D016212:Transforming Growth Factor beta; D019444:Vaccines, DNA; C074119:heat-shock protein 65, Mycobacterium; D016753:Interleukin-10; D007371:Interferon-gamma; D018833:Chaperonins