Variation of human natural killer cell phenotypes with age: Identification of a unique KLRG1-negative subset

Human natural killer (NK) cells subsets are phenotypically characterized by their lack of CD3 and low/high expression of CD56. This study revealed an age-associated increase in the ratio of CD3−CD56dim to CD3−CD56bright NK cells, whereas distinct expression patterns of CD2, CD16, CD57, and the C-type lectin family members killer cell lectin–like receptor −D1 (CD94) and −G1 (KLRG1), were noted on both these NK and the CD3+CD56+ T cell subsets; moreover, CD94 and KLRG1 expression were significantly reduced with age. Although the proportion of CD3−CD56bright NK cells vs CD3−CD56dim cells decreased with age, the percentage of CD3−CD56bright cells expressing IFN-γ after activation significantly increased, potentially representing compensatory augmentation of cytokine production to maintain the important immunoregulatory role of these cells in older individuals. Collectively, these results highlight new evidence for a continuum of change during immunologic aging and present unique data for variation of NK cell subsets with human aging.