Killer-cell inhibitory receptors, CD158a/b, are upregulated by interleukin-2, but not interferon-gamma or interleukin-4

ALTHOUGH it is now accepted that killer-cell inhibitory receptors (KIRs), w hich were molecularly cloned in 1995, deliver negative signals to natural k iller (NK) cells regarding the recognition of target cells, it is still unc lear how the expression of these receptors on lymphocytes is regulated. The refore, we investigated the regulation of expression of representative KIRs , CD158a and CD158b, by cytokines such as interleukin-a (IL-2), IL-4 and in terferon-gamma (IFN-gamma). Neither IL-4 nor IFN-gamma affected the express ion of CD158a/b, but incubation for 48 h with IL-2, which enhances the kill er activity of Mt cells, upregulated the expression of the KIRs, This upreg ulation by IL-2 was also observed in CD16-positive cells sorted from total lymphocytes. In contrast, IL-4, which is a down-regulator of IL-2-induced k iller responses, did not change the level of CD158a/b expression when added after the IL-2 treatment. These findings suggest that IL-2 plays an import ant role in the regulation of CD158a/b expression, and might be involved in controlling NK activity via regulating expression of these molecules.