As. Diamond et Rg. Gill, An essential contribution by IFN-gamma to CD8(+) T cell-mediated rejectionof pancreatic islet allografts, J IMMUNOL, 165(1), 2000, pp. 247-255
CD8(+) T cells have long been considered to be the prototypical cytotoxic l
ymphocyte subpopulation. However, whether alloreactive CD8(+) T cells requi
re traditional cytolytic pathways such as perforin and Fas ligand (FasL) to
mediate graft rejection has been a controversial issue. In the present stu
dies, we examined the role of varied effector pathways in CD8(+) T cell-med
iated rejection of pancreatic islet allografts, Our goal was to systematica
lly determine the relative requirements, if any, of perforin and Fast as we
ll as the proinflammatory cytokine IFN-gamma in triggering graft destructio
n. To study CDS' T cell effector pathways independently of other lymphocyte
populations, purified alloreactive CD8(+) T cells were adoptively transfer
red into severe combined immune-deficient (SCID) recipients bearing establi
shed islet allografts, Results indicate that to reject established islet al
lografts, 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-media
ted rejection of established islet allografts, Furthermore, alloreactive CD
8(+) TCR transgenic T cells (2C) also show IFN-gamma dependence for mediati
ng islet allograft rejection in vivo. We speculate from these results that
the production of IFN-gamma by alloreactive CD8(+) T cells is a rate-limiti
ng step in the process of islet allograft rejection.