Age-related changes in natural killer cell receptors from childhood throughold age

ABSTRACT

Most studies on natural killer (NK) cells and aging have focused on overall cell numbers and global cytotoxicactivity. NK cell functions are controlled by surface receptors belonging to three major families killer cellimmunoglobulin-like receptors (KIRs), natural cytotoxicity receptors (NCRs), and C-type lectins. The expressionof these receptors was investigated from childhood through old age in T, NKT- andNKcells and also in theCD56dim (cytotoxic) and CD56bright (responsible for cytokine production) NK cell subsets. A decrease in theexpression of activating receptors (NKp30 and NKp46) was observed in NK cells in elderly individuals. KIRexpression was increased only in the CD56bright subset. Children presented similar results regarding expressionof NKp30 and KIR, but not NKp46.NKG2Dexpression was decreased in T cells of elderly subjects. Analysisof KIR genotype revealed that KIR2DL5 and KIR2DS3 were significantly associated with old age. Cytotoxicactivity was preserved from childhood through old age, suggesting that the increase of the absolute numberof CD56dim, observed in elderly, may represent a compensatory mechanism for the receptor expressionalterations. This initial study provides the framework for more focused studies of this subject, which arenecessary to determine whether the changing balance of NK receptor expression may influence susceptibilityto infectious, inflammatory, and neoplastic diseases.(AU)