IL-4 regulates IL-2 induction of lymphokine-activated killer activity from human lymphocytes.
IL-4 is a pluripotent lymphokine acting on various cell types. We investigated the role of human IL-4 on the generation of lymphokine-activated killer (LAK) activity. Human IL-4 alone did not induce LAK activity and inhibited IL-2 induction of LAK activity from unstimulated PBMC, peripheral blood null cells, spleen cells, and lymph node cells in a dose-dependent manner. IL-4 also inhibited several phenomena induced by IL-2 such as cell proliferation, augmentation of NK activity, increase of Leu-19+ cells, and expression of IL-2R(p55) on either CD3+ or Leu-19+ cells. IL-4, however, augmented cell proliferation with other T cell mitogens including PHA, Con A, PMA, or allo-MHC Ag with or without IL-2. In contrast to unstimulated cells, IL-4 alone induced marked cell proliferation and LAK activity as well as Leu-19+ cells from in vitro IL-2 preactivated PBMC or null cells, and did not inhibit IL-2 induced cell proliferation, LAK activity, Leu-19+ cells and IL-2R(p55) expression, but rather augmented them with low doses of IL-2. Although IL-4 alone induced LAK activity from peripheral blood of some patients previously given IL-2, IL-4 inhibited in vitro LAK generation with IL-2 from these cells in most cases. Therefore, IL-4 appears to directly inhibit the IL-2 activation pathway via IL-2R(p70) and prevent resting LAK precursors from proliferating and differentiating into final effector cells. However, once cells were sufficiently preactivated by IL-2, IL-4 induced LAK activity and did not inhibit IL-2 activation of these cells. These data suggest an immunoregulatory role of IL-4 on human null cells and T cells.
Kawakami
Y
Y
Division of Cancer Treatment, National Cancer Institute, Bethesda, MD 20892.
Custer
M C
MC
Rosenberg
S A
SA
Lotze
M T
MT
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D001685:Biological Factors / Q000494:pharmacology; D016207:Cytokines; D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D004357:Drug Synergism; D006131:Growth Inhibitors / Q000494:pharmacology; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology / Q000627:therapeutic use; D015847:Interleukin-4; D007378:Interleukins / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000276:immunology; D007700:Kinetics; D008213:Lymphocyte Activation / Q000187:drug effects*; D008214:Lymphocytes / Q000145:classification / Q000276:immunology*; D008221:Lymphoid Tissue / Q000276:immunology; D010641:Phenotype
D000276:Adjuvants, Immunologic; D001685:Biological Factors; D016207:Cytokines; D006131:Growth Inhibitors; D007376:Interleukin-2; D007378:Interleukins; D015847:Interleukin-4