The 60-kDa heat shock protein modulates allograft rejection

Allograft rejection is a process of immune reactivity triggered by foreign transplantation antigens. We now demonstrate that the 60-kDa heat shock pro tein (hsp60), a molecule that is identical in the donor and the recipient, can regulate allograft immunity. In wild-type mice, hsp60 expression was gr eatly enhanced in allografts being rejected. By using MHC class II (Ecu) pr omoter hsp60 transgenic mice either as donors of skin with enhanced express ion of hsp60, or as allograft recipients with decreased hsp60 autoimmunity, we found that augmented expression of mouse hsp60 in the allograft acceler ated its rejection, whereas reduced autoimmunity to mouse hsp60 in graft re cipients delayed the process. Moreover, in nontransgenic mice, therapeutic administration of hsp60 or hsp60 peptides, known to modulate naturally occu rring hsp60 autoimmunity, led to delayed allograft rejection. Thus, we demo nstrate that hsp60 expression and hsp60 autoimmunity can influence and modi fy the immune response to foreign antigens. Hence, autoimmunity to self-hsp 60 epitopes is not necessarily an aberration, but may serve physiologically and therapeutically to modulate foreign immunity.