1Internal Medicine Department, Sohag Faculty of Medicine, South Valley University, Sohag, Egypt, ²The Carlos and Marguerite Mason Transplantation Research Center Renal Division, Department of Medicine and Veterans Affairs Medical Center, Atlanta, GA, USA and ³Pathology and Laboratory Medicine, Veterans Affairs, Medical Center and State University of New York, Buffalo, NY, USA.

In this study we examined the role of endogenous IFNg in the induction of long-term allograft acceptance. We found that IFNg is essential for long term survival of vascularized cardiac allografts induced by treating mice with B7-CD28 T cell costimulation blockade alone or in combination donor antigen administration. To investigate the in vivo mechanisms by which IFNg facilitates the induction of allograft acceptance, we examined T lymphocyte proliferation and apoptosis in wild-type (IFNg ^+/+) and IFNg gene knockout (IFNg ^-/-) mice challenged with allogeneic cells. We found that alloantigen-induced T cell proliferation is significantly greater in IFNg ^-/- than IFNg ^+/+ mice. Moreover, B7-CD28 T cell costimulation blockade alone or in combination with donor splenocyte transfusion abrogated alloantigen-induced T cell proliferation in IFNg ^+/+ mice but failed to do so in IFNg ^-/- mice. These treatment regimens increased activation-induced apoptosis of T lymphocytes in both IFNg ^+/+ and IFNg ^-/- mice. Donor splenocyte transfusion alone did not alter T cell proliferation or apoptosis. These data suggest that (a) IFNg facilitates the induction of long-term allograft survival by limiting the proliferation of alloactivated T lymphocytes, and (b) B7-CD28 T cell costimulation blockade exerts immunosuppressive actions by inhibiting the proliferation of activated T lymphocytes and by promoting their apoptosis in vivo.