Circulating NK cell subsets and NKT-like cells in renal transplant recipients with acute T-cell-mediated renal allograft rejection

Emerging evidence indicates that natural killer (NK) cells and NKT-like cells may affect allograft outcomes following solid organ transplantation. However, the roles of these cells in allograft acceptance and dysfunction are controversial. To assess the changes in NK cell and CD3(+)CD56(+) NKT-like cell frequency and phenotype in renal allograft recipients and to explore their associations with acute T-cell-mediated renal allograft rejection (ACR), longitudinal changes in NK and NKT-like cell frequency and phenotype were characterized using flow cytometry and immunohistochemistry in the peripheral blood and kidney allograft tissues in 142 recipients undergoing kidney transplantation. The serum concentrations of NK cell-associated cytokines were also detected by cytokine multiplex immunoassay. In contrast to the healthy controls, recipients with stable graft function exhibited increased proportions of CD56(bright)CD16(dim) subsets and decreased proportions of NKT-like cells in their peripheral blood mononuclear cells (PBMCs). Patients with ACR demonstrated increased proportions of NK cells, which were associated with increased CD3(-)CD56(bright) subsets and decreased CD3(-)CD56(dim) subsets, an increase in the CD56(bright)/CD56(dim) ratio in PBMCs and increased CD56(+) NK cell infiltration in the kidney allograft, compared with the stable controls. In addition, there was a decreased proportion of NKT-like cells in patients with ACR, and an increased ratio of CD56(bright)/NKT-like cells compared with the stable controls. These differences appeared to be consistent with the increase in the serum concentrations of C-C motif chemokine 19 and the decrease in the serum concentrations of interleukin-15. These data indicate that CD56(bright) NK cells may promote the development of ACR, and that NKT-like cells may have immunoregulatory function. The results also imply that the CD56(bright)/CD56(dim) ratio may affect the ACR signatures.