CD56dim Natural Killer Cells
المؤلف:
Hoffman, R., Benz, E. J., Silberstein, L. E., Heslop, H., Weitz, J., & Salama, M. E.
المصدر:
Hematology : Basic Principles and Practice
الجزء والصفحة:
8th E , P218-219
2025-12-07
43
CD56dim NK cells are strongly cytolytic and are able to kill infected as well as tumor cell targets without prior sensitization. They constitutively express the interleukin-2/15 (IL-2/IL-15) receptor (R) β- and common γ-receptor chains, which together form a receptor complex through which cells may respond to stimulation following exposure to either IL-2 or IL-15.14,15 CD56dim NK cells can lyse tumor cell targets through at least three distinct mechanisms. First, they can execute cytotoxicity through the exocytosis of lytic granules containing the pore-forming protein perforin and proteases called granzymes (e.g., granzyme B or GrzB) which initiate an apoptotic program via cleavage of specific protein substrates. Second, cytotoxicity can be mediated through NK cell expression of Fas ligand (CD95L) and TNF-related apoptosis-inducing ligand (TRAIL) which interact with their respective receptors CD95/Fas and TRAIL-R1 and -R2 on the target cell surface. This binding event leads to recruitment of the Fas-associated protein with death domain (FADD), recruitment and activation of procaspase 8 and 10, and the initiation of a caspase cascade that results in target cell apoptosis. This process is associated with NK cell production of cytokines, IFN-γ, TNF-α, and GM-CSF. Third, CD56dim NK cells can mediate antibody dependent cytotoxicity (ADCC) via the high-level surface expression of CD16 (FcγRIIIA), a low-affinity receptor for IgG which mediates a lytic program against antibody-coated target cells. Compared with CD56bright NK cells, freshly isolated, unstimulated CD56dim NK cells have intrinsically greater cytotoxicity in vitro against NK-sensitive tumor targets such as the well-studied K562 chronic myelogenous leukemia cell line, and they exhibit relatively high surface density expression of killer-cell immunoglobulin-like receptors (KIRs), a family of polymorphic activating and inhibitory receptors that are critically important in regulating NK cell surveillance of host tissues for cells with “altered self”.
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