Cytokine sensitivity of human NK cells during immunosenescence. 2. IL2-induced interferon gamma secretion

A majority of natural killer (NK) cells constitutively express intermediate affinity IL2 receptors made of beta gamma chains and respond by way of enhanced cytokine secretion. However, alterations in cytokine sensitivity of purified NK cells with respect to cytokine secretion during immunosenescence have not been examined before. In view of the major immunomodulatory role of IL2 and the anti-tumor effects of interferon gamma (IFN-gamma), we have investigated the recombinant human IL2-induced NK cell secretion of IFN-gamma in vitro. After an 18-h activation period, the secretion of IFN-gamma by the peripheral blood NK cells 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. Under similar conditions, purified T cells did not respond to IL2. However, the sensitivity of NK cells to the same inductive ligand, IL2, towards a different function i.e., cytotoxic activity, was not significantly impaired in the aged. It is possible that the cytokine secretory deficiency of senescent NK cells might be an additional mechanism which could favor the establishment of tumors and viral infections in the elderly. However, as discussed here, our findings do offer alternate explanations and a potential target for experimental immunotherapy.