Immunosenescence of Human Natural Killer Cells

Abstract

Natural killer (NK) cells are a key component of innate immunity involved not only in the elimination of virus-infected or tumor cells but also in the regulation of the immune response by producing cytokines and chemokines that can activate other cellular components of innate and adaptive immunity. NK cell subsets are differentially affected by aging. Whereas CD56^bright cells are decreased in healthy elderly individuals, the CD56^dim subset is expanded. The expression of CD57, a marker of highly differentiated NK cells, is increased in the elderly; this supports the notion that a remodeling process of NK cell subsets occurs in aging with a gradual decrease in more immature CD56^bright NK cells and an increase in highly differentiated CD56^dim CD57+ NK cells. This NK cell redistribution can explain many of the phenotypic and functional changes in NK cells associated with healthy aging such as decreased proliferation and the maintenance of CD16-dependent cytotoxicity.

Nutritional and Physical Activity Interventions to Improve Immunity

“…16 Immunosenscence is characterized by impaired function of immune cell populations and an ''overcrowding'' of the so-called immune space whereby the population of leukocyte subsets essential in responses to novel pathogens (naïve T lymphocytes), have been gradually replaced by expanded clones (effector and effector-memory T lymphocytes) that have a late-stage differentiation phenotype and limited antigenic specificity. 13,15,[17][18][19] An increased inflammatory status has also been associated with the ageing process (inflamm-aging) which may give rise to other health issues in the older population (cardiovascular disease , Type 2 diabetes). 20 Immunosenescence is a primary factor contributing to increased infection susceptibility and decreased response to vaccinations in the elderly.…”

The Innate Immune System and Aging: What is the Contribution to Immunosenescence ?

“…This decreased production of cytokines contributes to the altered activation of macrophages with aging resulting in decreased microbicidal and tumoricidal activities. Thus, NK cells of elderly show decreased proliferative response to cytokines, higher cytotoxic capacity under certain cytokine stimulations including IL-2, IL-12 or IFNγ and a higher sensitivity to stimulation via CD16 [89,90]. The cytotoxic activity of NK cells with aging is depending whether the whole population of NK cells is considered or on per cell basis.…”

“…NKp30 has been also shown to be important in the regulation of the cross-talk between NK cells and DCs. The ligation of this receptor by an unknown ligand on DCs can lead either to a direct killing of DCs by NK cells or to the secretion of IFN-γ and TNF-α and the subsequent maturation of DCs [90]. By this interaction the NK cells can activate the DCs to more efficiently prime T cells.…”

“…The total number of NK cells is increasing with aging [93] which could be a compensatory mechanism in the aging immune system [94] however the subset distribution is changed with aging as the number of NK cells with CD56 dim increases, while those with CD56 bright decreases [84,85,90]. Furthermore, the expression of CD57 is increased on CD56 dim NK cells from elderly subjects presenting a highly differentiated subset of NK cells.…”

Investigating the potential immune role of fish NCAMs: Molecular cloning and expression analysis in mandarin fish

“…As the surface marker of human NK cells [10], CD56's expression level is related to its functional division. CD56 bright subset, indicating a less mature state, is common in lymph organs and with strong cytokine-secreting ability, whereas the CD56 dim subset, indicating a more mature state, is numerous in peripheral blood and more cytotoxic functionally [11].…”