NK and NK/T cells in human senescence

Natural killer (NK) cells are cytotoxic cells that play a critical role in the innate immune response against infections and tumors. Recent studies on NK cell biology have demonstrated that besides their cytotoxic function, N K cells express cytokine and chemokine receptors and also that they secrete other immunoregulatory cytokines and chemokines, supporting their relevanc e in the regulation of the immune response by promoting downstream adaptive , Th1 mediated, responses against infections. Immunosenescence is the deter ioration of the immune response associated with aging. It is characterized mainly by a defective T cell response, but includes changes in the number a nd function of other cells of the innate immune system. Age-associated alte rations in the number and function of NK cells have been reported. There is a general consensus that a progressive increase in the percentage of NK ce lls with a mature phenotype occurs in elderly donors associated with an imp airment of their cytotoxic capacity when considered on a "per cell" basis. The response of NK cells from elderly individuals to IL-2, or other cytokin es is also decreased in terms of proliferation, expression of CD69 and kill ing of NK-resistant cell lines. Furthermore early IFN-gamma and chemokine p roduction in response to IL-2 or IL-12 is also decreased. However aging doe s not significantly alter other NK cell functions such as TNF-alpha product ion or perforin induction in response to IL-2. The percentage of T cells th at co-express NK cell markers is also increased in aging. These results ind icate chat the increase in the number of "classical" mature NK and NK/T cel ls in aging is associated with a defective functional capacity of NK cells. Low NK cell number or function in elderly individuals is associated with i ncreased mortality risk and increased incidence of severe infections. suppo rting the role of NK cells in the defense against infections in the elderly . (C) 2000 Elsevier Science Ltd. All rights reserved.