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Differential Roles of CD8 + and CD8 − T Lymphocytes in Corneal Allograft Rejection in ‘High‐Risk’ Hosts
Author(s) -
Niederkorn J.Y.,
Stevens C.,
Mellon J.,
Mayhew E.
Publication year - 2006
Publication title -
american journal of transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.89
H-Index - 188
eISSN - 1600-6143
pISSN - 1600-6135
DOI - 10.1111/j.1600-6143.2006.01237.x
Subject(s) - cytotoxic t cell , cd8 , medicine , immunology , perforin , corneal transplantation , fas ligand , immune system , transplantation , biology , apoptosis , in vitro , programmed cell death , biochemistry
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.