CD56bright cells differ in their KIR repertoire and cytotoxic features from CD56dim NK cells

Abstract

In this study we present new differential characteristics of NK cells expressing CD56 surface antigen in low (CD56dim) or high (CD56bright) density. In contrast to CD56bright NK cells CD56dim cells express killer cell immunoglobulin (Ig)‐like receptors (KIR) such as CD158a, CD158b, and NKB1. However, c‐type lectin‐like receptors (KLR) CD94/NKG2 and CD161 are present on both subsets. The ability to form conjugates with susceptible targets is approximately twice as strongly pronounced in CD56dim vs. CD56bright NK cells. Last but not least, granules of CD56dim cells contain about tenfold more perforin and granzyme A enabling potentially more effective cytolysis compared to CD56bright NK cells. On the other hand, CD56bright NK cells are superior in producing the proinflammatory cytokines IFN‐γ (28.5% vs. 20.8%, p<0.05) and TNF‐α (28% vs. 15.8%, p<0.001). The differentNK cell populations retained their specific phenotype in vitro during culture in the presence of IL‐2 contradicting that they simply display different stages of maturity. Taken together our data support the view that CD56bright cells are specialized NK cells that regulate immunological response mechanisms rather by cytokine supply than by their cytotoxic potential. The poor cytolyticcapacity of CD56bright NK cells can be explained by weak ability in forming conjugates with target cells and low contents of perforin and granzyme A in their granules.

Primary Human Tumor Cells Expressing CD155 Impair Tumor Targeting by Down-Regulating DNAM-1 on NK Cells

“…Patient characteristics are described in supplemental Table I. 4 Peritoneal effusions and peripheral blood samples were obtained with informed consent. Blood from healthy donors was obtained from the Blood Centre at the Karolinska University Hospital.…”

“…Human NK cells can be divided into two main functional subsets based on the intensity of CD56 expression (2). Although there is a degree of functional overlap, CD56 dim NK cells have a potent cytotoxic function, whereas perforin low CD56 bright NK cells are thought to have immunoregulatory properties (2)(3)(4)(5). Recent data support the notion that CD56 bright and CD56 dim NK cells represent different stages of maturation, with CD56 dim NK cells being the more differentiated cell type (6).…”

KIR2DL5 alleles mark certain combination of activating KIR genes

“…14 KIR2DL5 displays a variegated distribution on the surface of CD56 dim NK cells, whereas the surface expression of KIR2DL4 appears to be restricted to the minority subset of KIR neg CD56 bright NK cells. 8,15 Although KIR2DL4 has been implicated in both inhibitory and activating functions, 6,[16][17][18] KIR2DL5 appears to be solely an inhibitory receptor. 7 Multiple sequences for both KIR2DL5A and KIR2DL5B loci have been characterized from individuals of different ethnic origins.…”

Virologically Suppressed HIV Patients Show Activation of NK Cells and Persistent Innate Immune Activation

“…NK cells in peripheral blood are commonly defined as belonging to one of two subsets. A minor CD56 bright CD16 2 subpopulation produces high quantities of cytokines, including IFN-g, in response to stimuli such as monocyte-derived IL-12 (13). The major CD56 dim CD16 + subset is more efficient at killing virus-infected or transformed host cells, and the expression of the Fcg receptor IIIA, CD16, on this subset enables it to perform ADCC.…”