Abstract
Purpose: :
The adaptive immune system and the recently discovered toll-like receptors, as members of the innate immune system, play an important role in the outcome of organ and tissue transplantation. The purpose of our study was to investigate the expression of TLR3, TLR5 and the contribution of CD3 (T cells), CD8 (cytotoxic T cells), CD163, CD11c (macrophages) positive cells in corneas with immunological graft rejection.
Methods: :
Ten corneas with graft rejection and 6 normal human corneas (controls) were analysed using digital microscopy and automated image analysis after immunostaining with monoclonal antibodies specific for the target antigens.
Results: :
In corneal epithelial cells TLR3 and TLR5 proteins were detected in 9 (90%) of the rejected samples and in 3 normal cases (50%). An increased number of CD3, CD8, CD163 and CD11c positive cells was seen in the epithelium of corneas with graft rejection as compared to controls.In the stroma, 7 corneas (70%) with graft rejection expressed TLR3 or TLR5, but stromal cells of controls were negative for both receptors. Large numbers of CD3, CD8, CD163 and CD11c positive cells could be detected in the stroma of rejected corneas, whereas these were almost missing from controls. In immunological graft rejection, endothelial cells could be analyzed in one single case, due to low number or lack of endothelial cells in other cases. Endothelial cells in the one case, were positive for TLR3 and TLR5 receptor along with some CD3 and CD8 positive lymphocytes. Normal human corneal endothelial cells expressed TLR5 (100%), but not TLR3 protein (0%) and were negative for the examined CD markers.
Conclusions: :
In corneas, TLR3 and TLR5 expression increases in epithelial and stromal cells in the course of immunological graft rejection. TLR3 expression is restricted to endothelial cells of corneas with graft rejection. The increased expression of TLR3 and 5 paralelled with the occurence of CD3, CD8, CD163 and CD11c positive cells, suggesting, that the immunological rejection is not restricted to endothelial cells, but also targets the epithelium.
Keywords: cornea: basic science • transplantation • immunohistochemistry