The 60-kDa Heat Shock Protein Modulates Allograft Rejection

• Published in: Proceedings of the National Academy of Sciences - PNAS 1999-04, Vol.96 (9), p.5159-5163
• Main Authors: Birk, Ohad S., Gur, Sara L., Elias, Dana, Margalit, Raanan, Mor, Felix, Carmi, Pnina, Bockova, Jana, Altmann, Daniel M., Cohen, Irun R.
• Format: Article
• Language: English
• Subjects: Animals; Antigens; Autoimmunity; Biological Sciences; Chaperonin 60 - biosynthesis; Chaperonin 60 - immunology; Chaperonin 60 - pharmacology; Epitopes; Graft rejection; Graft Rejection - immunology; Graft Rejection - metabolism; Homologous transplantation; Immune system; Immunology; Mice; Mice, Transgenic; Molecules; Proteins; Reactivity; Skin Transplantation; T lymphocytes; Transgenic animals; Transplantation, Homologous; Transplants & implants; Vaccination
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.96.9.5159

Allograft rejection is a process of immune reactivity triggered by foreign transplantation antigens. We now demonstrate that the 60-kDa heat shock protein (hsp60), a molecule that is identical in the donor and the recipient, can regulate allograft immunity. In wild-type mice, hsp60 expression was greatly enhanced in allografts being rejected. By using MHC class II (Eα) promoter hsp60 transgenic mice either as donors of skin with enhanced expression of hsp60, or as allograft recipients with decreased hsp60 autoimmunity, we found that augmented expression of mouse hsp60 in the allograft accelerated its rejection, whereas reduced autoimmunity to mouse hsp60 in graft recipients delayed the process. Moreover, in nontransgenic mice, therapeutic administration of hsp60 or hsp60 peptides, known to modulate naturally occurring hsp60 autoimmunity, led to delayed allograft rejection. Thus, we demonstrate that hsp60 expression and hsp60 autoimmunity can influence and modify the immune response to foreign antigens. Hence, autoimmunity to self-hsp60 epitopes is not necessarily an aberration, but may serve physiologically and therapeutically to modulate foreign immunity.