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.