Role of Early Chemokine Production and Inflammatory Cell Recruitment in High Risk Corneal Transplants

Abstract

Abstract: : Purpose: To characterize the role of early chemokine production and inflammatory cell recruitment into the cornea following syngeneic and allogeneic high risk corneal transplantation. Methods: Orthotopic syngeneic (C57BL/6 to C57BL/6) and allogeneic (Balb/c to C57BL/6) corneal grafts were performed in high risk vascularized recipients. Corneal extracts from corneal buttons harvested at 6, 24, 48, 72 hrs, 5, 7 and 14 days after transplantation were prepared and chemokine/cytokine production was assessed using Luminex technology. The recruitment of neutrophils, macrophages and T cells into the host corneal bed and corneal transplant was assessed and quantified by immunohistochemical staining using CD11b, F4/80, NIMPR–14, CD4 and CD8 antibodies. Results: In both, syngeneic and allogeneic high risk corneal transplants, there is an influx of neutrophils and macrophages early on after transplantation. The recruitment of these population of cells correlated with the production of CXC and CC chemokines. Interesting, a population of CD4 positive cells could be detected mainly in the host bed of allogeneic high risk grafts by day 7 after transplantation. Moreover, IP–10, a CXC chemokine responsible for the recruitment of activated T cells, was significantly produced at higher levels during the first 3 days after transplantation in high risk allogeneic grafts only. This correlated with the recruitment and persistence of CD4 T cells in the host bed. Conclusions:. Early recruitment of innate inflammatory cells after transplantation in high rik recipients is similar in syngeneic and allogeneic grafts in response to chemokine production associated with surgical trauma. However, IP–10 production is only produced in allogeneic grafts and this could represent the chemoattractant signal responsible the recruitment of activated alloantigenic CD4 T cells responsible for graft rejection.

Keywords: immunomodulation/immunoregulation • transplantation • immune tolerance/privilege