The effects of IL-4 on human natural killer cells. A potent regulator of IL-2 activation and proliferation.
NK cells are directly activated by rIL-2 and subsequently undergo rIL-2-dependent proliferation in vitro. Herein, we report that rIL-4 is a potent regulator of human NK cells. Although rIL-4 had no effect on the cytotoxic activity of resting NK cells, it was capable of inhibiting in a concentration-dependent manner the rIL-2-induced cytolytic activation of NK cells against NK cell-resistant tumor cell targets. rIL-4 acted directly on NK cells and did not require accessory cells. rIL-4-induced inhibition of NK cell activation was specific for rIL-2 in that activation of NK cell cytolysis by IFN-alpha was not affected. These results represent the first direct evidence that rIL-2 and IFN-alpha activate NK cells by different pathways. rIL-4 also effectively blocked the rIL-2-dependent proliferation of NK cells. The results presented in this study clearly demonstrate that rIL-4 is a potent regulator of IL-2-dependent mechanisms of NK cell activation and proliferation and thus may play an important physiologic role in vivo.
Nagler
A
A
Becton-Dickinson Monoclonal Center, Inc., Mountain View, CA 94043.
Lanier
L L
LL
Phillips
J H
JH
D002460:Cell Line; D003110:Colonic Neoplasms / Q000276:immunology; D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007376:Interleukin-2 / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D015847:Interleukin-4; D007378:Interleukins / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000276:immunology; D004915:Leukemia, Erythroblastic, Acute / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects*; D011994:Recombinant Proteins / Q000494:pharmacology
D007166:Immunosuppressive Agents; D007376:Interleukin-2; D007378:Interleukins; D011994:Recombinant Proteins; D015847:Interleukin-4