Acute rejection of vascularized heart allografts in the absence of IFN gamma

It is generally assumed that IFN gamma plays a central role in acute allograft rejection. To test this hypothesis, we transplanted fully allogeneic (MHC class I and II incompatible) C3H/H3J (H2(k)) murine hearts to IFN gamma(-/-) (IFN gamma gene-knockout) and IFN gamma(+/+) BALB/c (H2(d)) mice. The phenotype of IFN gamma(-/-) mice was confirmed by demonstrating absent IFN gamma protein production by Con A stimulated IFN gamma(-/-) splenocytes. Both IFN gamma(-/-) and IFN gamma(+/+) strains rejected transplanted hearts acutely: graft survival (mean +/- SD) ws 5.2+/-0.4 and 6.0+/-0.0 days, respectively. Histologic examination revealed similar patterns of acute cellular rejection in both mouse groups. IFN gamma mRNA was present in hearts rejected by IFN gamma(+/+) mice but was absent in those rejected by IFN gamma(-/-) mice. IL-2, IL-4, IL-10, and TNF alpha mRNA expression, on the other hand, we similar in grafts rejected by either strain. We also observed that hapten-induced delayed-type hypersensitivity (DTH) response was significantly reduced but not absent in IFN gamma(-/-) mice. Our results demonstrate that IFN gamma is not required for acute cellular rejection of fully allogeneic murine hearts. We propose that non-DTH mechanisms of allograft destruction could be enhanced in the absence of IFN gamma and thus lead to robust acute rejection.