Interleukin-4 differentially regulates interleukin-2-mediated and CD2-mediated induction of human lymphokine-activated killer effectors.
Natural killer (NK) cells can be differentiated into lymphokine-activated killer (LAK) effectors following stimulation with interleukin (IL)-2. This induction can be negatively regulated by IL-4. In this study, we demonstrate that the stimulation of NK cells through the CD2 pathway with (9-1 + 9.6) monoclonal antibodies can also induce these cells to secrete tumor necrosis factor-alpha (TNF-alpha) and to differentiate into LAK effectors. More importantly, our data indicate that, in contrast to the IL-2-induced LAK generation, the anti-CD2-triggered LAK activity was not regulated by IL-4. IL-4 was found to enhance the LAK activity as well as NK cell proliferation following activation with anti-CD2 by a mechanism involving, at least in part, an increased TNF-alpha production. Using immobilized monoclonal antibodies against the Fc receptor (Fc gamma RIII or CD16) for NK stimulation, we also observed that the anti-CD16-induced LAK activity was not inhibited by IL-4. These data further point to a pivotal role of TNF-alpha as a regulatory cytokine in anti-CD2-induced LAK generation, and suggest that IL-4 could serve as a discriminatory factor between two distinct pathways involved in the activation of non-MHC-restricted cytotoxicity.
Laboratoire d'Immunologie, URA 1156 CNRS, Villejuif, France.
E
E
Robinet
M
M
Kamoun
F
F
Farace
S
S
Chouaib
D000945:Antigens, Differentiation, T-Lymphocyte / Q000502:physiology*; D018801:CD2 Antigens; D002478:Cells, Cultured; D006801:Humans; D007376:Interleukin-2 / Q000502:physiology*; D015847:Interleukin-4 / Q000494:pharmacology*; D015979:Killer Cells, Lymphokine-Activated / Q000502:physiology*; D008213:Lymphocyte Activation; D017452:Receptors, IgG / Q000502:physiology; D011971:Receptors, Immunologic / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D000945:Antigens, Differentiation, T-Lymphocyte; D018801:CD2 Antigens; D007376:Interleukin-2; D017452:Receptors, IgG; D011971:Receptors, Immunologic; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4