CYTOKINE SENSITIVITY OF HUMAN NK CELLS DURING IMMUNOSENESCENCE .2. IL2-INDUCED INTERFERON-GAMMA SECRETION

A majority of natural killer (NK) cells constitutively express interme diate affinity IL2 receptors made of beta gamma chains and respond by way of enhanced cytokine secretion. However, alterations in cytokine s ensitivity of purified NK cells with respect to cytokine secretion dur ing immunosenescence have not been examined before. In view of the maj or immunomodulatory role of IL-2 and the anti-tumor effects of interfe ron gamma (IFN-gamma), we have investigated the recombinant human IL2- induced NK cell secretion of IFN-gamma in vitro. After an 18-h activat ion period; the secretion of IFN-gamma by the peripheral blood NK cell s from the elderly was severely impaired at 80 U/ml of IL2 and above. At an optimal dose of IL2 (960 U/ml), NK cells from young and elderly showed a mean 11- and 3-fold increase in secretion, respectively. Unde r similar conditions, purified T cells did not respond to IL2. However , the sensitivity of NK cells to the same inductive ligand, IL2, towar ds a different function i.e., cytotoxic activity, was not significantl y impaired in the aged. It is possible that the cytokine secretory def iciency of senescent NK cells might be an additional mechanism which c ould favor the establishment of tumors and viral infections in the eld erly. However, as discussed here, our findings do offer alternate expl anations and a potential target for experimental immunotherapy.