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Dai Miyazaki, Yoshitsugu Inoue, Yu–Feng Yao, Annabelle A. Okada, Yoshikazu Shimomura, Kozaburo Hayashi, Yasuo Tano, Yuichi Ohashi; T-Cell–Mediated Immune Responses in Alloepithelial Rejection after Murine Keratoepithelioplasty. Invest. Ophthalmol. Vis. Sci. 1999;40(11):2590-2597.
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purpose. To evaluate the role of delayed-type hypersensitivity (DTH) and
cytotoxic T-lymphocyte (CTL) responses on alloepithelial rejection in a
murine keratoepithelioplasty model.
methods. C3H/He mouse corneal lenticules were grafted around the limbus in
BALB/c mice, and alloepithelial rejection was assessed by microscopic
evaluation. The relation between rejection scores and DTH or CTL
responses to donor antigens was assessed by Spearman correlation
analysis. Suppression of DTH responses by induction of anterior
chamber–associated immune deviation (ACAID) was used to evaluate the
contribution of DTH responses to allograft rejection. CTL responses
were evaluated by in vitro and in vivo depletion of CD4+ or
results. DTH responses, which developed 2 weeks postoperatively,
correlated significantly with rejection scores (correlation coefficient r = 0.55). ACAID induction by anterior chamber
inoculation of C3H/He splenocytes significantly suppressed allospecific
DTH responses and alloepithelial rejection. While allospecific CTL
responses also developed 2 weeks postoperatively and increased by 4
weeks, CTL responses did not exhibit positive correlation with
rejection scores (r = −0.36, P = 0.076). The CTL responses were mediated exclusively by
CD8+ cells. Although in vivo depletion of CD8+ cells abolished the induction of CTL responses, it did not prevent
allograft rejection. Immunohistochemistry showed infiltration of
CD4+ and CD8+ cells into the alloepithelium.
Positive staining for interferon γ but not interleukin 4 further
implicated the participation of a DTH response.
conclusions. Allograft rejection after keratoepithelioplasty appears to be mediated
primarily by DTH responses, with CTL responses playing only a minor
role perhaps in modifying the development of
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