CD4+ T-cell-independent rejection of corneal allografts

Jerry Y. Niederkorn, Christina Stevens, Jessamee Mellon, Elizabeth Mayhew

Research output: Contribution to journalArticlepeer-review

39 Scopus citations


Background. Several studies suggest that a significant number of corneal allografts undergo rejection in the absence of CD4+ T cells. This study examined the role of CD4+ T cell-independent mechanisms of corneal allograft rejection. Methods. BALB/c corneal allografts were transplanted to C57BL/6 beige nude mice that received either CD8- or CD8+ T cells from C57BL/6 CD4 knockout (KO) mice that had rejected BALB/c corneal allografts. Immune effector functions of CD8- or CD8+ T cells from C57BL/6 CD4 KO mice were assessed using delayed-type hypersensitivity assays and Annexin V apoptosis assays respectively. Results. Both CD8- and CD8+ T cells from CD4 KO corneal allograft rejector mice mediated corneal allograft rejection following adoptive transfer to nude mice. CD8- T cells, but not CD8+ T cells, from CD4 KO mice adoptively transferred donor-specific DTH and induced apoptosis of BALB/c corneal endothelial cells in vitro. Apoptosis of BALB/c corneal endothelial cells was mediated by double negative (DN) T cells, as treatment of CD8- cells from CD4 KO mice with anti-Thy 1.2 plus complement abolished their effector function. Conclusion. The results support the proposition that CD4+ T cell-independent rejection of corneal allografts can be mediated by either CD8+ or CD8- T cells. The CD8- T cells represent a unique DN T cell population that might mediate rejection by either direct cytolysis or by inducing apoptosis of the donor corneal endothelium.

Original languageEnglish (US)
Pages (from-to)1171-1178
Number of pages8
Issue number8
StatePublished - Apr 2006


  • Apoptosis
  • CD4 T cells
  • Corneal allograft
  • Double-negative T cells

ASJC Scopus subject areas

  • Transplantation


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