CD4+ T-cell-mediated mechanisms of corneal allograft rejection: Role of Fas-induced apoptosis

Sushma Hegde, Clay Beauregard, Elizabeth Mayhew, Jerry Y. Niederkorn

Research output: Contribution to journalArticle

70 Scopus citations

Abstract

Background. The role of CD4+ T cells as effector cells in corneal allograft rejection is poorly understood. We investigated the role of CD4+ T cells as helper cells in the generation of allospecific effector macrophages in corneal graft rejection and the role of CD4+ T cells as apoptosis-inducing effector cells. Methods. Corneal allografts were transplanted to CD4 knockout, FasL-deficient, and macrophage-depleted hosts. An Annexin-V binding assay was used to evaluate the susceptibility of corneal cells to both Fas-dependent and CD4+ T-cell-mediated apoptosis in vitro. Results. Macrophages were essential for graft rejection, but not as effector cells. Anti-BALB/c CD4+ T cells from immunized C57BL/6 mice induced apoptosis of BALB/c corneal epithelial and endothelial cells. However, anti-BALB/c CD4+ T cells from FasL-deficient gld/gld mice did not induce apoptosis of BALB/c corneal endothelial cells. Moreover, gld/gld mice had a reduced capacity to reject BALB/c corneal allografts. Although the initial results suggested a role for Fas-induced apoptosis in corneal graft rejection, additional experiments indicated otherwise. The incidence and tempo of immune rejection of Fas-deficient Ipr/Ipr corneal allografts were no different than those for corneal grafts from Fas-bearing C57BL/6 donors. Moreover, CD4 + T-cell-mediated apoptosis of corneal cells could not be blocked with either Fas-Fc fusion protein or anti-FasL blocking antibody. Conclusions. The results suggest that CD4+ T cells function directly as effector cells and not as helper cells in the rejection of corneal allografts. Although the corneal endothelium is highly susceptible to Fas-induced apoptosis, this is apparently not the primary mechanism of CD4+ T-cell-dependent rejection.

Original languageEnglish (US)
Pages (from-to)23-31
Number of pages9
JournalTransplantation
Volume79
Issue number1
DOIs
Publication statusPublished - Jan 15 2005

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Keywords

  • Apoptosis
  • CD4 T helper cells
  • Corneal allograft
  • Immune privilege

ASJC Scopus subject areas

  • Transplantation
  • Immunology

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