Role of T Cell Chemoattractants CXCL10/IP10 and CXCL9/Mig in High Risk Corneal Allograft Transplantation

Abstract

Purpose: : We have previously reported that the T cell chemoattractants, CXCL10/IP10 and CXCL9/Mig, are up regulated in high risk corneal allografts after transplantation. The goal of this work is to understand how these regulate the kinetics of graft rejection.

Methods: : Fully MHC mismatched corneal allografts (Balb/c to C57BL6) were performed in vascularized high risk recipients treated with anti-CXCL9 or anti CXCL10 antibody or control. Graft survival was monitored and quantification of infiltrating inflammatory cells was performed by immunohistochemistry. T cell priming data was also gathered by ELISPOT.

Results: : High risk corneal allograft rejection associated with the neutralization of CXCL10 correlated with an increased recruitment of macrophages and T cells into the corneal allograft. Neutralization of CXCL10/IP10 induced graft rejection was not associated with differences in T cell priming. Interestingly and similar to CXCL10/IP10 neutralization data, neutralization of the other produced T cell chemoattractant CXCL9/Mig, resulted in increased high risk corneal allograft rejection.

Conclusions: : Our data suggests that the role of T cell chemoattractant production by high risk corneal allografts may have a regulatory effect on the recrutiment of T cells that results in graft protection rather than rejection.

Keywords: cytokines/chemokines • immunomodulation/immunoregulation • transplantation