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Sushma Hegde, Jerry Y. Niederkorn; The Role of Cytotoxic T Lymphocytes in Corneal Allograft Rejection. Invest. Ophthalmol. Vis. Sci. 2000;41(11):3341-3347.
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purpose. Immunologic rejection constitutes a major barrier to the success of
allogeneic corneal transplants, but the specific mediators and
mechanisms of graft rejection are poorly understood. Several studies
have implicated cytotoxic T-lymphocyte (CTL) responses, typically
associated with CD8+ T cells, in promoting corneal graft
rejection. This study sought to test the hypothesis that CTLs are
essential in promoting corneal graft rejection.
methods. BALB/c donor corneas were grafted orthotopically onto C57BL/6, perforin
knockout, or CD8+ T-cell knockout mice. The tempo and
incidence of graft rejection were observed for each group. In separate
experiments, donor-specific CTL and delayed-type hypersensitivity (DTH)
responses were tested at the time of graft rejection by a standard
chromium release assay and an ear swelling assay, respectively.
results. Perforin knockout and CD8+ T-cell knockout mice were as
effective as wild-type C57BL/6 control mice in rejecting BALB/c donor
corneas. Furthermore, animals in all three groups were found to develop
robust donor-specific DTH, not CTL, responses at the time of graft
rejection. Histopathologically, the rejected corneas from all three
groups contained a predominantly mononuclear cellular infiltrate.
conclusions. This study rejects the hypothesis that CD8+ CTLs are
essential in promoting corneal graft rejection and instead further
implicates donor-specific DTH reactions as the relevant immune response
during graft failure.
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