title: Human tumor-induced and naturally occurring Treg cells differentially affect NK cells activated by either IL-2 or target cells.
abstract: NK cells play a crucial role in the eradication of tumor cells. Naturally occurring (n) Treg cells and induced (i) Treg cells are two distinct Treg subsets. While the interaction of nTreg cells with NK cells has been investigated in the past, the role of tumor iTreg cells in the modulation of NK-cell function remains unclear. Tumor iTreg cells were generated from CD4(+) CD25(-)  T cells in the presence of autologous immature DCs, head and neck cancer cells and IL-2, IL-10, and IL-15. The effect of iTreg cells and nTreg cells on the expression of NKG2D, NKp44, CD107a, and IFN-γ by NK cells, as well as NK tumor-cytolytic activity, were investigated. iTreg cells - similar to recombinant TGF-β and nTreg cells - inhibited IL-2-induced activation of NK cells in the absence of target cell contact. Surprisingly, and in contrast to nTreg cells, iTreg cells enhanced NK-cell activity elicited by target cell contact. The cytolytic activity of NK cells activated by iTreg cells was mediated via perforin and FasL. We conclude that tumor iTreg cells inhibited IL-2-mediated NK-cell activity in the absence of target cells, whereas the tumoricidal activity of NK cells was enhanced by iTreg cells. Our data suggest a complex, previously not recognized, differential regulation of human NK activity by iTreg cells in the tumor microenvironment.
authors: Department of Otorhinolaryngology, University of Duisburg - Essen, Essen, Germany.
authors: Christoph
authors: C
authors: Bergmann
authors: Clarissa A
authors: CA
authors: Wild
authors: Mustafa
authors: M
authors: Narwan
authors: Ramin
authors: R
authors: Lotfi
authors: Stephan
authors: S
authors: Lang
authors: Sven
authors: S
authors: Brandau
mesh_terms: D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D053222:Fas Ligand Protein / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D007376:Interleukin-2 / Q000276:immunology* / Q000378:metabolism / Q000494:pharmacology; D020014:K562 Cells; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D055655:NK Cell Lectin-Like Receptor Subfamily K / Q000276:immunology / Q000378:metabolism; D055629:Natural Cytotoxicity Triggering Receptor 2 / Q000276:immunology / Q000378:metabolism; D054353:Perforin / Q000276:immunology / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000276:immunology / Q000378:metabolism
chemical_list: D015703:Antigens, CD; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D007376:Interleukin-2; C527085:KLRK1 protein, human; C112837:NCR2 protein, human; D055655:NK Cell Lectin-Like Receptor Subfamily K; D055629:Natural Cytotoxicity Triggering Receptor 2; D016212:Transforming Growth Factor beta; D054353:Perforin; D007371:Interferon-gamma