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In humans, NK cells are identified by the expression of the common hematopoietic cell marker CD45 and the more specific glycoprotein designated as CD56 [21, 31]. They do not express CD3. It has been shown in humans that mature cytotoxic NK cells are also developing in situ from resident oligopotent CD34⁺CD45RA⁺ hematopoietic precursor cells in the lymph nodes and liver [21, 33, 34]. About 90% of circulating human NK cells express T-bet^hi, Eomes^lo, CD56^dim, and CD16^hi characteristics that are considered as mature and highly cytotoxic [15, 35]. The remaining 10% of human PBMC-derived NK cells are T-bet^hi, Eomes^hi, CD56^bright, and CD16^lo. This subpopulation of NK cells produces a lot of cytokines (notably including IFNγ and TNFα) and is less cytotoxic than the CD16^bright, CD56^dim predominant phenotype. A fine balance between activation or inhi­bition of NK cell responses depends on the expression and communication between type I Ig superfamily activating receptors (NKG2D) and type II C-type lectin inhibitory receptors (NKG2A/CD94) [36–38].

Tissue-specific NK cells express the above-mentioned molecules at various levels. Most tissues in humans contain more of the immature, cytokine-producing, CD56^bright, CD16^dim NK cells [39, 40]. These NK cells present in the spleen and liver express the C-X-C motif-containing chemokine receptor 6 (CXCR6) [41]. This chemokine receptor has a ligand CXCL16 which is implicated in the homing to and survival within the liver of NK cells at quiescent state [41]. Furthermore, in humans, these NK cells express the already mentioned T-bet and Eomes as well as the CD69 activation marker [15].

Recently, it has been demonstrated that a subpopulation of NK cells so called “memory-like NK cells” exist, bearing various receptors including NKG2C and CD57 (CD16^bright, CD56^dim, CD57⁺) [38]. It is of note that this population was described in relation to human CMV infection [42], a mechanism somewhat similar to the increase in proportions of CD8 T cells specific for CMV epitopes [43, 44]; however, the temporal and spatial features of its accumulation are still not completely resolved.