Interferon-gamma is necessary for initiating the acute rejection of major histocompatibility complex class II-disparate skin allografts

Background. Although interferon (IFN)gamma has immunostimulatory functions, it is not essential for the acute rejection of fully allogeneic grafts in mice. It is not known whether IFN gamma plays a critical role in the acute rejection of MHC class I- or MHC class II-disparate allografts. Methods. We studied the survival of skin allografts transplanted from fully allogeneic (BALB/c), MHC class I-disparate (bm1), or MHC class ZI-disparat e (bm12) donors to C57BL/6 wild-type (IFN gamma(+/+)) and IFN gamma gene-kn ockout (IFN gamma(+/+)) recipients. We also investigated the in vitro respo nses of IBN gamma(+/+) and IFN gamma(-/-) T cells to MHC class II-disparate splenocytes. Results. We found that IFN gamma(-/-) recipients reject BALB/c and bm1 skin grafts at the same rate as IFN gamma(+/+) mice but are not capable of reje cting bm12 skin. Despite the inability of IFN gamma(-/-) mice to reject bm1 2 skin grafts, IFN gamma(-/-) T cells displayed vigorous proliferation and cytotoxic responses when stimulated with bm12 splenocytes in vitro. Further more, priming IFN gamma(-/-) recipients with bm12 splenocytes enabled these mice to reject bm12 skin grafts at a normal rate and to mount a cutaneous delayed-type hypersensitivity response to the bm12 antigen. Conclusion. The data demonstrate that IFN gamma is not necessary for genera ting effector mechanisms associated with acute transplant rejection but tha t it is required for initiating alloimmune responses to MHC class II dispar ate skin grafts.