An essential contribution by IFN-γ to CD8+ T cell-mediated rejection of pancreatic islet allografts

CD8(+) T cells have long been considered to be the prototypical cytotoxic lymphocyte subpopulation. However, whether alloreactive CD8(+) T cells require traditional cytolytic pathways such as perforin and Fas ligand (FasL) to mediate graft rejection has been a controversial issue. In the present studies, we examined the role of varied effector pathways in CD8(+) T cell-mediated rejection of pancreatic islet allografts, Our goal was to systematically determine the relative requirements, if any, of perforin and Fast as well as the proinflammatory cytokine IFN-gamma in triggering graft destruction. To study CDS' T cell effector pathways independently of other lymphocyte populations, purified alloreactive CD8(+) T cells were adoptively transferred into severe combined immune-deficient (SCID) recipients bearing established islet allografts, Results indicate that to reject established islet allografts, primed CD8(+) T cells do not require the individual action of the conventional cytotoxic effecters perforin and Fas ligand, In contrast, the ability to produce IFN-gamma is critical for efficient CD8(+) T cell-mediated rejection of established islet allografts, Furthermore, alloreactive CD8(+) TCR transgenic T cells (2C) also show IFN-gamma dependence for mediating islet allograft rejection in vivo. We speculate from these results that the production of IFN-gamma by alloreactive CD8(+) T cells is a rate-limiting step in the process of islet allograft rejection.