Differential roles of CD8+ and CD8- T lymphocytes in corneal allograft rejection in 'high-risk' hosts.
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.
Department of Ophthalmology, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA. jerry.niederkorn@utsouthwestern.edu
J Y
JY
Niederkorn
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C
Stevens
J
J
Mellon
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E
Mayhew
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D016039:Corneal Transplantation / Q000276:immunology*; D053222:Fas Ligand Protein; D006084:Graft Rejection / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D013601:T-Lymphocytes / Q000276:immunology; D048069:Tumor Necrosis Factors / Q000235:genetics / Q000276:immunology
D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D048069:Tumor Necrosis Factors; D054353:Perforin