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K. Engelmann, F. Wang, F. Koch–Nolte; Investigation About T Lymphocyte Activation by Human Corneal Cell Types . Invest. Ophthalmol. Vis. Sci. 2005;46(13):2804.
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Purpose: Corneal graft failure is often related to graft rejection, and T cells may be involved in this rejection process. T cell activation requires two distinct signals from antigen presenting cells. The aim of the present study was to investigate T cell activation by corneal cells. Methods: In a first step expression of HLA antigens was studied in cultured human corneal endothelial and epithelial cells. In a second step the human corneal cells were co–cultured with peripheral blood cells. Activation of T lymphocytes purified from peripheral blood cells was analysed by immunohistochemical staining and FACS analysis. Additionally to the cell culture experiments, human corneal grafts that were exchanged after transplant failure were investigated. Results: HLA expression occurs in corneal epithelial and endothelial cells. Therefore these cells may serve as antigen presenting cells. Co–culture of corneal epithelial or endothelial cells with peripheral blood cells led to expression of CD69, a marker for activated T cells. Furthermore expression of CD80 and CD86 was found on human corneal epithelial cells. Human corneal endothelial cells expressed only CD80 but not CD86. CD80 and CD86 may serve as the second signal for T cell activation. Another molecule that can serve as the required second signal for T cell activation is CD154, a ligand of CD40. This molecule could be detected on human corneal epithelial cells only after prolonged co–culture time of six days. Investigations on rejected corneal grafts revealed that CD4 positive T cells participate in corneal graft rejection. Furthermore, CD40 positive cells were determined in the superficial epithelium. Conclusions: Human corneal epithelial cells may participate in the corneal transplant rejection process as potential antigen presenting cells. They are capable of activating T lymphocytes by expressing costimulatory molecules which participate in T lymphocyte activation, such as CD80, CD86, CD40, CD154. Corneal transplant rejection may be initiated by corneal epithelial cell contact with T lymphocytes. The results are consistent with former report that cytotoxic T cells (CD8+) play no essential role in rejection of orthotopic corneal allografts in mice.
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