Fig. 2

Differences in marker expression between CD56^bright NK cells and CD56^dim NK cells. Under homeostatic conditions, CD56^bright NK cells and CD56^dim NK cells express a variety of activation, functional and migratory markers that can be used to differentiate them, but also to explain their different locations and functions. In general, CD56^bright NK cells express higher levels of immunoregulatory proteins, such as tumor necrosis factor (TNF), interferon-γ (IFN-γ), granzyme K, natural killer group (NKG)2A, natural cytotoxicity receptors (NCR), and they express the trimeric high-affinity receptors for IL-2. In contrast, CD56^dim NK cells express the dimeric low-affinity receptor for IL-2 and higher levels of cytotoxic proteins, such as granzyme B and perforin. With regards to chemokine receptors, CD56^bright NK cells express C–C chemokine receptors (CCR)2, CCR5, CCR7, C–X–C motif chemokine receptor (CXCR)3, and CXCR4, while CD56^dim NK cells express CXCR1, CX3CR1, chemokine receptor (ChemR)23, and sphingosine-1-phosphate receptor 5 (S1P5), and low levels of CXCR3 and CXCR4. Furthermore, CD56^bright NK cells generally express higher levels of adhesion molecules lymphocyte function-associated antigen 2 (LFA-2) and CD62L (L-selectin), whereas CD56^dim NK cells preferentially express LFA-1 [59, 60, 65]. Both subsets express similar levels of very late antigen-4 (VLA-4) [61]. However, the expression of chemotactic receptors and adhesion molecules can be strongly affected by external stimuli