Abstract
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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 3341-3347 |
| Number of pages | 7 |
| Journal | Investigative Ophthalmology and Visual Science |
| Volume | 41 |
| Issue number | 11 |
| State | Published - 2000 |
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ASJC Scopus subject areas
- Ophthalmology
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The role of cytotoxic T lymphocytes in corneal allograft rejection. / Hegde, S.; Niederkorn, J. Y.
In: Investigative Ophthalmology and Visual Science, Vol. 41, No. 11, 2000, p. 3341-3347.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - The role of cytotoxic T lymphocytes in corneal allograft rejection
AU - Hegde, S.
AU - Niederkorn, J. Y.
PY - 2000
Y1 - 2000
N2 - 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.
AB - 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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M3 - Article
VL - 41
SP - 3341
EP - 3347
JO - Investigative Ophthalmology and Visual Science
JF - Investigative Ophthalmology and Visual Science
SN - 0146-0404
IS - 11
ER -