CD8 T cells can reject major histocompatibility complex class I-deficient skin allografts

Following transplantation, recipient T cells can recognize and respond to donor antigens expressed directly on donor cells, and can respond to donor-derived peptides that have been processed and presented in the context of recipient MHC through the indirect pathway. Indirectly primed CD4(+) T cells have been well studied in transplantation, but little information is available regarding whether indirectly primed CD8(+) T cells participate in rejection. To address this, we placed MHC class I-deficient D(b)K(b) knockout skin grafts onto allogeneic H-2 (k) SCID recipients followed by adoptive transfer of purified H-2 (k) CD8(+) T cells. The MHC class I-deficient grafts were rejected and only CD8(+) T cells were detectable in the recipient lymphoid organs and in the skin grafts. Immunohistochemical analysis showed that CD8(+) T cells were found in close proximity to vascular endothelial cells and to recipient infiltrating macrophages, suggesting specific interactions. The data demonstrate that cross-primed polyclonal CD8(+) T cells can function as active participants in the effector phase of rejection. The findings confirm and extend previous studies using a monoclonal TCR transgenic T cell and shed light on mechanisms of acute and chronic graft injury that are potentially relevant to human transplant recipients.