CELLULAR IMMUNOLOGY 145, l-10 (1992) The Impairment of Natural Killer Function in the Healthy Aged Is Due to a Postbinding Deficient Mechanism M. VITALE,*,~ L. ZAMAI,* L. M. NERI,$ A. GALANZI,* A. FACCHINI,~ R. RANA, 11 A. CATALDI, 11 AND S. PAPAWS zyxwvutsrqponmlkjihgfedcbaZYX *Istitnto di Anatomiu Umana Normaie. Bologna: jlstituto di Citomorjtilogia N.P. CNR c/o Istituto di Ricerca Codivilla-Putti. Bologna; $lstituto di Anatomia Umana Normale, Ferrara: $Lab Immttnologia e genetica IOR, la Clinica Medica, Universitri di Bologna; lllstituto di Morfologia Umana, Chieti; and Plstituto di Science Mocfologiche, Urbino, Italy Received January 22, 1992; accepted July 1, 1992 In order to study the fine mechanisms that underlie the impairment of non-MHC-restricted cytolytic activity which occurs during human aging, we examined by multiparametric flow cy- tometry the binding and lytic activities of human natural killer cells. The flow analysis revealed a striking increase of the CD16Y subset, together with a significant decrease of CD@‘“@” cells and total T cells (CD3+). Aging had no influence on the CDS“‘” subset. The total lytic activity expressed by PBL as well as their binding efficiency to K562 targets were moderately but not significantly increased in the elderly. In contrast, the cytotoxicity of the single target-bound natural killer cell (i.e., iytic efficiency) was deeply impaired in aged subjects, suggesting that the NK functional impairment observed in aging is located at postbinding level. 8 1992 Academic Press. zyxwvutsrqponml IIIC. INTRODUCTION During the past decade, the cytolytic function of lymphoid subpopulations in the elderly has been investigated to define a possible immunological defect that could explain the occurrence of some pathological conditions (i.e., infections and neoplasia) (l-3). Nevertheless, the study of the phenotype and function of mononuclear cells in aging has yielded conflicting results (4). The most striking evidence of age-related decline of the immune system includes a reduced number of circulating T cells (5- 7) a decreased proliferative response to mitogens (8, 9) and a reduced production of lymphokines and their receptors (10). On the other hand, other investigators reported only slight or hardly any modification of lymphocyte phenotype and function (6, 11, 12). We have previously described the main phenotypic changes that occur in peripheral blood during aging as a decrease of CD3’ cells and an increase of the CD16+ and CD57’ cells (2). The rise in circulating NK cells in the elderly was not associated with an increase in the natural cytotoxicity against K562 tumor cells, suggesting an im- pairment of NK function in the elderly. In contrast, other groups described an increase of NK function with aging (3, 13-15). The divergence of these findings can be partly due to the different techniques employed to evaluate the binding and killing activities of NK cells to tumor targets (2). We have recently described two methodologies in flow cytometry for the identifi- cation of the single lymphoid subsets involved in the binding to K562 tumor targets 000%8749/92 $5.00 Copyngbt 0 1992 by Academic Press. Inc. All rights of reproduction ,n any form reserved.