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 CXCR5IFN-gammaCD8 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 CXCR5IFN-gammaCD8 T cells (p=0.01) and significantly lower ratios of CXCR5IFN-gammaCD8 T cell to combined CD4 Th1/Th2 cell subsets (IFN-gammaCD4 and IL-4CD4 cells; p=0.0001) compared to recipients who remained DSA-negative over the first year posttransplant. CONCLUSION: Our data raise the possibility that human CXCR5IFN-gammaCD8 T cells are a homologue to murine CXCR5IFNgammaCD8 T cells (termed antibody-suppressor CD8 T cells) and that the quantity of CXCR5IFN-gammaCD8 T cells (or the ratio of CXCR5IFN-gammaCD8 T cells to Th1/Th2 CD4 T cells) may identify recipients at risk for development of DSA.