Aging Aging

NK Cell Function in Aging 31123Age-Related Alterationsto Natural Killer Cell FunctionErminia Mariani, Corona Alonso, and Rafael Solana1. IntroductionHuman natural killer (NK) cells represent a heterogeneous lymphoid populationinvolved in the recognition and lysis of tumor and virally infected cells.NK cells are defined by the expression of the IgG Fc receptor CD16 (FcγRIIIA)and/or CD56. NK cells do not rearrange immunoglobulin (Ig) or T-cell receptor(TCR) genes. Therefore, neither Ig nor the TCR–CD3 complex is expressedat the cell surface, except for the zeta (ζ) chain. Both markers, CD16 and CD56,have been used to analyze age-associated changes in the number of NK cells.The most characteristic function of NK cells is non-major histocompatibilitycomplex (MHC) restricted cytotoxicity of tumor cell lines and killing oftarget cell lines, in particular the erythroleukemia cell line K562. The effect ofaging on NK cytotoxicity has been extensively studied. NK cytotoxicity isbased on the interaction between the NK effector cells and target cells, usuallycell lines that do not express HLA class I antigens on the surface. Several stepscan be differentiated in the cytotoxic assays. The first is conjugate formation,in which NK cells binds the target cell. In a second phase of NK cell triggering,activation signals are transmitted from the cell surface inside the cells. As aresult perforin granules are reoriented to the effector–target contact site, andthey are finally released and the target cell lysed.The K562 cell line is the target cell most commonly used for measuringlysis by resting NK cells from elderly people, whereas the NK-resistant Daudicell line is used for testing the cytotoxic capacity of activated NK cells. BothDaudi or P815, a mastocytoma murine cell line that is also resistant to lysis byFrom: Methods in Molecular Medicine, Vol. 38: Aging Methods and ProtocolsEdited by: Y. A. Barnett and C. R. Barnett © Humana Press Inc., Totowa, NJ311