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Human tumor‐induced and naturally occurring Treg cells differentially affect NK cells activated by either IL‐2 or target cells
Author(s) -
Bergmann Christoph,
Wild Clarissa A.,
Narwan Mustafa,
Lotfi Ramin,
Lang Stephan,
Brandau Sven
Publication year - 2011
Publication title -
european journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.272
H-Index - 201
eISSN - 1521-4141
pISSN - 0014-2980
DOI - 10.1002/eji.201141532
Subject(s) - biology , nk 92 , interleukin 21 , nkg2d , interleukin 12 , lymphokine activated killer cell , microbiology and biotechnology , cytolysis , il 2 receptor , janus kinase 3 , perforin , immunology , cancer research , cytotoxic t cell , immune system , in vitro , t cell , cd8 , biochemistry
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.