Effect of recombinant interferon gamma and interleukin-2 and of a monoclonal antibody against interferon gamma on the rat immune response against heart allografts

We studied the effect of rat rec-IFN-γ, human rec-IL-2, and an IgG1 monoclonal antibody (DB1) directed against rat IFN-γ on allograft survival in the rat in various experimental conditions. The DB1 monoclonal antibody did not prolong heart allograft survival in the (LEW/BN)F1 to LEW combination, even when used at high doses (2 mg/rat x 9 days). Rec-IFN-γ induced major histocompatibility antigen expression in vivo, but its administration had no effect on graft survival either of untreated LEW recipients of (LEW x BN)F1 heart allografts or of donor blood-transfused LEW recipients. In addition, rec-IFN-γ alone had no effect on graft survival in cyclosporine-treated rats. In contrast, rec-IL-2 shortened heart allograft survival both in untreated and in cyclosporine-treated recipients. Rec-IFN-γ partially reversed the effects of rec-IL-2 in cyclosporine-treated rats. The data suggest that in vivo administration of IFN-γ in allograft recipients may have a suppressor effect, in addition to the postulated augmenting effect on the immune response by increasing MHC antigen expression.