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.
Drobyski
W R
WR
Department of Medicine, Medical College of Wisconsin, Milwaukee 53226.
LeFever
A V
AV
Truitt
R L
RL
D015703:Antigens, CD / Q000378:metabolism; D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism; D001853:Bone Marrow / Q000187:drug effects / Q000276:immunology; D001854:Bone Marrow Cells; D017252:CD3 Complex; D019002:CD56 Antigen; D002448:Cell Adhesion / Q000187:drug effects; D002469:Cell Separation; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D006801:Humans; D007376:Interleukin-2 / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D015847:Interleukin-4 / Q000494:pharmacology*; D015979:Killer Cells, Lymphokine-Activated / Q000187:drug effects* / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects*; D010641:Phenotype; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D013601:T-Lymphocytes
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D019002:CD56 Antigen; D007376:Interleukin-2; D011948:Receptors, Antigen, T-Cell; D011994:Recombinant Proteins; D015847:Interleukin-4