Journal
AMERICAN JOURNAL OF TRANSPLANTATION
Volume 6, Issue 4, Pages 705-713Publisher
BLACKWELL PUBLISHING
DOI: 10.1111/j.1600-6143.2006.01237.x
Keywords
apoptosis; cornea; CTL; DTH; FasL; keratoplasty
Categories
Funding
- NEI NIH HHS [EY07641, EY016664] Funding Source: Medline
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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.
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