We recently reported that a novel CXCR5+IFN-γ+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.
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.
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-γ+CD8+ T cells (P = 0.01) and significantly lower ratios of CXCR5+IFN-γ+CD8+ T cell to combined CD4+ Th1/Th2 cell subsets (IFN-γ+CD4+ and IL-4+CD4+ cells; P = 0.0001) compared to recipients who remained DSA-negative over the first-year posttransplant.
Our data raise the possibility that human CXCR5+IFN-γ+CD8+ T cells are a homolog to murine CXCR5+IFN-γ+CD8+ T cells (termed antibody-suppressor CD8+ T cells) and that the quantity of CXCR5+IFN-γ+CD8+ T cells (or the ratio of CXCR5+IFN-γ+CD8+ T cells to Th1/Th2 CD4+ T cells) may identify recipients at risk for development of DSA.