Apoptosis and allograft rejection in the absence of CD8(+) T cells

Background. The requirement for cytotoxic T lymphocytes during allograft re jection is controversial. We previously demonstrated that CD8(+) T cells ar e not necessary for allograft rejection or for the induction of apoptosis i n rat small intestinal transplantation. In this study, we examined the mech anisms of apoptosis: and rejection after liver transplantation in the absen ce of CD8(+) T cells. Methods. Either Lewis or dark agouti rat liver grafts were transplanted int o Lewis recipients to create syngeneic and allogeneic combinations. CD8(+) T cells were depleted in an additional allogeneic group by treatment with O X-8 mAb on day -1 and day 1 after liver transplant. Results. Apoptosis and rejection were observed in both the CD8(+) T cell-de pleted allogeneic and allogeneic grafts by hematoxylin and eosin staining, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling stain ing, and radiolabeled-annexin V in vivo imaging. Granzyme B and FasL were e xpressed in all allogeneic transplants, including those depleted of CD8(+) T cells, indicating that a mononuclear cell other than a CD8(+) T cell can be the source of these molecules during allograft rejection. Activation of the caspase cascade was detected in all rejecting allografts, Caspases 3, 8 , and 9 were activated at similar significantly elevated levels in both all ogeneic and CD8(+) T cell-depleted liver grafts. Conclusion. These data indicate that in the absence of CD8(+) T cells an al ternative pathway, associated with granzyme B and FasL expression and activ ation of the caspase cascade, can mediate apoptosis and graft rejection.