Ionomycin treatment renders NK cells hyporesponsive

Natural killer cells are cytotoxic lymphocytes important in immune responses to cancer and multiple pathogens. However, chronic activation of NK cells can induce a hyporesponsive state. The molecular basis of the mechanisms underlying the generation and maintenance of this hyporesponsive condition are unknown, thus an easy and reproducible mechanism able to induce hyporesponsiveness on human NK cells would be very useful to gain understanding of this process. Human NK cells treated with ionomycin lose their ability to degranulate and secrete IFN-γ in response to a variety of stimuli, but IL-2 stimulation can compensate these defects. Apart from reductions in the expression of CD11 a/CD18, no great changes were observed in the activating and inhibitory receptors expressed by these NK cells, however their transcriptional signature is different to that described for other hyporesponsive lymphocytes.This work was supported by grants from the Fondo de Investigación Sanitaria (PI11/00298 and PI08/1701), MINECO (SAF2014-58752-R) (to HTR), a JAE Predoc studentship from the CSIC and an EMBO Short term fellowship (to GRC) and the Intramural Research Program at the National Institutes of Health, National Institute of Allergy and Infectious Disease.Peer Reviewe