The biology of human natural killer-cell subsets.

Human natural killer cells: a unique innate immunoregulatory role for the CD56bright subset

Human NK Cell Education by Inhibitory Receptors for MHC Class I

CD56bright natural killer cells are present in human lymph nodes and are activated by T cell–derived IL-2: a potential new link between adaptive and innate immunity

Human natural killer (NK) cells can be subdivided into different populations based on the relative expression of the surface markers CD16 and CD56. The two major subsets are CD56(bright) CD16(dim/) (-) and CD56(dim) CD16(+), respectively. In this review, we will focus on the CD56(bright) NK cell subset. These cells are numerically in the minority in peripheral blood but constitute the majority of NK cells in secondary lymphoid tissues. They are abundant cytokine producers but are only weakly cytotoxic before activation. Recent data suggest that under certain conditions, they have immunoregulatory properties, and that they are probably immediate precursors of CD56(dim) NK cells. CD56(bright) NK cell percentages are expanded or reduced in a certain number of diseases, but the significance of these variations is not yet clear.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1365-2567.2008.03027.x

CD56bright natural killer (NK) cells: an important NK cell subset

Natural killer (NK) cells are components of the innate immune system that can recognize and kill virally infected cells, tumor cells, and allogeneic cells without prior sensitization. NK cells also elaborate cytokines (e.g., interferon-gamma and tumor necrosis factor-alpha) and chemokines (e.g., macrophage inflammatory protein-1alpha) that promote the acquisition of antigen-specific immunity. NK cell differentiation is accompanied by the cell surface expression of a mucin-like glycoprotein bearing an NK cell-restricted keratan sulfate-related lactosamine carbohydrate, the PEN5 epitope. Here, we report that PEN5 is a post-translational modification of P-selectin glycoprotein ligand-1 (PSGL-1). The PEN5 epitope creates on PSGL-1 a unique binding site for L-selectin, which is independent of PSGL-1 tyrosine sulfation. On the surface of NK cells, the expression of PEN5 is coordinated with the disappearance of L-selectin and the up-regulation of Killer cell Ig-like Receptors (KIR). These results indicate that NK cell differentiation is accompanied by the acquisition of a unique carbohydrate, PEN5, that can serve as part of a combination code to deliver KIR(+) NK cells to specific tissues.

Olivier Spertini

Papers

Modification of P-selectin glycoprotein ligand-1 with a natural killer cell-restricted sulfated lactosamine creates an alternate ligand for L-selectin