Inverse Association Between the Quantity of Human Peripheral Blood CXCR5+IFN-γ+CD8+T cells with De Novo DSA Production in the First Year After Kidney Transplant.

Background. We recently reported that a novel CXCR5(+)IFN-gamma(+)CD8(+) T-cell subset significantly inhibits posttransplant alloantibody production in a murine transplant model. These findings prompted the current study to investigate the association of human CD8(+) T cells with the same phenotype with the development of de novo donor-specific antibody (DSA) after kidney transplantation. Methods. In the current studies, we prospectively and serially analyzed peripheral blood CD8(+) and CD4(+) T-cell subsets and monitored for the development of de novo DSA in kidney transplant recipients during the first-year posttransplant. We report results on 95 first-time human kidney transplant recipients with 1-year follow-up. Results. Twenty-three recipients (24.2%) developed de novo DSA within 1-year posttransplant. Recipients who developed DSA had significantly lower quantities of peripheral CXCR5(+)IFN-gamma(+)CD8(+) T cells (P = 0.01) and significantly lower ratios of CXCR5(+)IFN-gamma(+)CD8(+) T cell to combined CD4(+) Th1/Th2 cell subsets (IFN-gamma(+)CD4(+) and IL-4(+)CD4(+) cells; P = 0.0001) compared to recipients who remained DSA-negative over the first-year posttransplant. Conclusions. Our data raise the possibility that human CXCR5(+)IFN-gamma(+)CD8(+) T cells are a homolog to murine CXCR5(+)IFN-gamma(+)CD8(+) T cells (termed antibody-suppressor CD8(+) T cells) and that the quantity of CXCR5(+)IFN-gamma(+)CD8(+) T cells (or the ratio of CXCR5(+)IFN-gamma(+)CD8(+) T cells to Th1/Th2 CD4(+) T cells) may identify recipients at risk for development of DSA.