CD4(+) T-cell-mediated mechanisms of corneal allograft rejection: role of Fas-induced apoptosis.

Autor:	Hegde S; Department of Ophthalmology, University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390, USA., Beauregard C, Mayhew E, Niederkorn JY
Jazyk:	angličtina
Zdroj:	Transplantation [Transplantation] 2005 Jan 15; Vol. 79 (1), pp. 23-31.
DOI:	10.1097/01.tp.0000147196.79546.69
Abstrakt:	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 lpr/lpr 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.
Databáze:	MEDLINE
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