Differential roles of CD8⁺ and CD8^- T lymphocytes in corneal allograft rejection in 'high-risk' hosts

We examined the role of perforin and FasL in corneal allograft rejection mediated by CD8⁺ and CD8^- T cells. BALB/c corneas were transplanted orthotopically into vascularized, 'high-risk' graft beds in C57BL/6 mice, perforin knockout mice and FasL-defective gld/gld mice. CD8⁺ and CD8^- T cells were collected following graft rejection and adoptively transferred to SCID mice, which were then challenged with BALB/c corneal allografts. In every case, CD8^- T cells could mediate graft rejection when adoptively transferred to SCID mice that received BALB/c corneal allografts. Although CD8⁺ T cells also mediated graft rejection, the tempo was slower. Moreover, CD8⁺ T cells collected FasL-defective donors that had rejected corneal allografts, mediated corneal allograft rejection in only 50% of the SCID mice that received the adoptively transferred cells. In some cases, CD8⁺ T-cell-mediated rejection occurred in the absence of delayed-type hypersensitivity and cytotoxic T-lymphocyte activity, but was associated with CD8⁺ T-cell-mediated apoptosis of BALB/c corneal cells in vitro. The results demonstrate the redundancy in immune mechanisms of corneal allograft rejection. Either CD8⁺ or CD8 ^- T cells can produce corneal allograft rejection, however functional FasL is necessary for optimal rejection, even in a high-risk setting.