Expansion of human NK-22 cells with IL-7, IL-2, and IL-1beta reveals intrinsic functional plasticity.
Natural killer-22 (NK-22) cells are a human NK cell subset situated in mucosal-associated lymphoid tissues that specialize in IL-22 secretion in response to IL-23. Here we investigated the cytokine requirements for NK-22 cell expansion. IL-7 maintained the survival of NK-22 cells and IL-22 production in response to IL-23 but was insufficient to induce robust expansion. Proliferation of NK-22 cells was increased markedly by adding either IL-1beta or IL-2 to IL-7 and was even stronger in the presence of IL-1beta plus IL-2. In contrast to IL-7, continuous culture in IL-1beta and IL-2 modified NK-22 cytokine profiles. IL-1beta promoted constitutive IL-22 secretion rather than acute IL-22 production in response to IL-23 and induced IL-17 in some cells. IL-2 reduced secretion of IL-22 and IL-17, increasing production of IFN-gamma and leukemia inhibitory factor. Functional deviation toward IFN-gamma production also was induced by continuous culture in IL-23. These results demonstrate the functional plasticity of NK-22 cells, which may allow flexible responses to different pathogens. Finally, we found that NK-22 cells released the B-cell survival factor, B-cell activating factor belonging to the TNF family (BAFF), suggesting a potential role of NK-22 cells in promoting B-cell-mediated mucosal immunity.
Department of Pathology and Immunology, Washington University School of Medicine, St Louis, MO 63110, USA.
Marina
M
Cella
Karel
K
Otero
Marco
M
Colonna
D053264:B-Cell Activating Factor / Q000096:biosynthesis; D001483:Base Sequence; D049109:Cell Proliferation / Q000187:drug effects; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D017931:DNA Primers / Q000235:genetics; D006801:Humans; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000096:biosynthesis; D053583:Interleukin-1beta / Q000494:pharmacology*; D007376:Interleukin-2 / Q000494:pharmacology*; D053760:Interleukin-23 Subunit p19 / Q000494:pharmacology; D015851:Interleukin-7 / Q000494:pharmacology*; D007378:Interleukins / Q000096:biosynthesis*; D007694:Killer Cells, Natural / Q000145:classification* / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D053605:Leukemia Inhibitory Factor / Q000096:biosynthesis; D016131:Lymphocyte Subsets / Q000145:classification* / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D014066:Palatine Tonsil / Q000166:cytology / Q000276:immunology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D000097043:Interleukin-22
D053264:B-Cell Activating Factor; D016207:Cytokines; D017931:DNA Primers; D007371:Interferon-gamma; D053583:Interleukin-1beta; D007376:Interleukin-2; D053760:Interleukin-23 Subunit p19; D015851:Interleukin-7; D007378:Interleukins; D053605:Leukemia Inhibitory Factor; D012333:RNA, Messenger; D011994:Recombinant Proteins; D000097043:Interleukin-22; C508594:IL2 protein, human; C508840:IL23A protein, human; C508605:IL7 protein, human; C507837:LIF protein, human; C505719:TNFSF13B protein, human