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

J. Y. Niederkorn, C. Stevens, J. Mellon, E. Mayhew

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)705-713
Number of pages9
JournalAmerican Journal of Transplantation
Volume6
Issue number4
DOIs
StatePublished - Apr 2006

Keywords

  • Apoptosis
  • CTL
  • Cornea
  • DTH
  • FasL
  • Keratoplasty

ASJC Scopus subject areas

  • Immunology and Allergy
  • Transplantation
  • Pharmacology (medical)

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