NK cells inhibit T-cell responses: LFA3+ but not LFA3- T-cell responses are suppressed.

There is increasing evidence that natural killer (NK) cells have immunoregulatory effects in addition to their ability to lyse tumour and virus-infected target cells. However, much of the evidence to date is based on the reported effect of adding relatively impure NK cell populations to various in vitro cultures, and the effect on T cells has been contradictory. Here we report the inhibitory effect of highly purified CD16+ NK cells on mixed lymphocyte reaction (MLR), using unseparated peripheral blood mononuclear cells (PBMC) and purified T cells as responders. Marked inhibition was observed (up to 75%) which was proportional to the number of CD16+ cells present, and was abrogated by ultraviolet irradiation. In contrast, the addition of CD16+ cells had no effect on the proliferative responses of five CD4+ anti-DR1 alloreactive T-cell clones. To test the relative sensitivity of previously primed versus virgin T cells to NK cell-mediated inhibition, freshly isolated T cells from PBMC were separated into LFA3+ (memory) and LFA3- (virgin) populations. CD16+ cells caused inhibition of proliferation of LFA3+ but not LFA3- cells in an MLR. In addition, the recall response of T cells to influenza was inhibited. These results further illustrate the regulatory potential of CD16+ NK cells, and suggest that previously primed cells are more susceptible to NK-mediated inhibition. However, activated (rather than resting) cells may escape regulation.