Regulation of lymphokine-activated killer activity in T-replete and T-cell-depleted human bone marrow by interleukin 4.

Donor-derived lymphokine-activated killer (LAK) cells appear to play a role in mediating an antileukemia effect in recipients of both T-replete and T-cell-depleted (TCD) bone marrow transplants. LAK activity, however, is subject to regulation by cytokines other than interleukin 2 (IL-2). The purpose of this study was to examine the effect of interleukin 4 (IL-4) on the induction of LAK activity in both T-replete and TCD bone marrow. IL-4 inhibited the induction of LAK activity in a time- and dose-dependent manner in both T-replete and TCD bone marrow cultures, although there appeared to be a differential effect, suggesting that T and non-T LAK precursors have different thresholds of sensitivity to IL-4. Single-cell cytotoxicity assays indicated that IL-4 did not inhibit binding of LAK effectors to targets but did reduce the frequency of lytic conjugates. Kinetic analysis techniques demonstrated that IL-4 decreased the maximal rate of target cell lysis by IL-2-activated LAK precursors and inhibited the rate of lytic programming. These data indicate that IL-4 is able to regulate the induction of LAK activity in both T-replete and TCD bone marrow and may play a role in modulating the generation of effector cells with potential antileukemia reactivity in vivo.