Serial changes in the expression of CXCR3 and CCR5 on peripheral blood lymphocytes following human renal transplantation

OBJECTIVES: In animal models of transplantation, chemokine receptors have been shown to direct the infiltration of T cells in immune responses and inflammation and to be critical in cellular recruitment. Although the chemokine receptors CXCR3 and CCR5 and their ligands have been found during acute rejection in transplanted human kidneys, the kinetics of expression on peripheral blood lymphocytes is unknown. MATERIALS AND METHODS: Using a whole-blood red-cell lysis fluorescence-activated cell sorter, serial expressions of CXCR3 and CCR5 on T-cell subsets were analyzed in 19 human renal transplant recipients following transplant. RESULTS: In patients developing allograft rejection (n=6), increased expression of CXCR3 occurred on the surface of CD4+ T cells by the third day after transplant. In patients remaining rejection free (n=13), decreased expression was seen. In patients experiencing allograft rejection and in those remaining rejection free, levels of CXCR3 on CD8+ T cells and CCR5 on CD4+ and CD8+ cells remained stable throughout the study. CONCLUSIONS: During allograft rejection, expression of CXCR3, but not CCR5, increases on peripheral CD4+ T cells prior to clinical evidence of allograft rejection and remains elevated for more than 2 weeks following transplantation. This may represent a specific molecular target for identifying and preventing allograft rejection.