MHC class I chain-related molecules induced on monocytes by IFN-gamma promote NK cell activation.
NKG2D receptor-ligand interaction triggers NK cell-mediated cytolysis and IFN-gamma secretion. IFN-gamma produced by NK cells has been found to promote the interaction between NK cells and monocytes; however, the underlying mechanism remains elusive. We demonstrate here that IFN-gamma exclusively induced or upregulated the expression of MHC class I chain-related (MIC) molecules, which are ligands of the NKG2D receptor, on the surface of human monocytes of the PBMC population. The IFN-gamma-induced MIC molecules on monocytes played an essential role in triggering the activation of NK cells because mAb-mediated masking of the MIC molecules and the inhibition of cell-to-cell contact using transwell inserts significantly abolished NK cell activation. Meanwhile, membrane-bound IL-15 (mIL-15) was concomitantly induced with MIC molecules on IFN-gamma-treated monocytes and played an essential role in protecting NK cells cocultured with monocytes from MIC-induced NKG2D down-modulation. Therefore, we conclude that the IFN-gamma-induced MIC molecules participated in monocyte/NK cell interaction and that this interaction also involved mIL-15.
Wang
Huiming
H
Institute of Immunology, PLA, The Third Military Medical University, Chongqing 400038, PR China.
Ruan
Zhihua
Z
Wang
Yiqin
Y
Han
Junfeng
J
Fu
Xiaolan
X
Zhao
Tingting
T
Yang
Di
D
Xu
Wenyue
W
Yang
Zhao
Z
Wang
Li
L
Chen
Yongwen
Y
Wu
Yuzhang
Y
D002450:Cell Communication; D002478:Cells, Cultured; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis* / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology*; D019409:Interleukin-15 / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology*; D008213:Lymphocyte Activation; D009000:Monocytes / Q000276:immunology*; D055655:NK Cell Lectin-Like Receptor Subfamily K; D011971:Receptors, Immunologic / Q000276:immunology / Q000378:metabolism; D055607:Receptors, Natural Killer Cell; D015854:Up-Regulation
D015395:Histocompatibility Antigens Class I; D019409:Interleukin-15; C527085:KLRK1 protein, human; D055655:NK Cell Lectin-Like Receptor Subfamily K; D011971:Receptors, Immunologic; D055607:Receptors, Natural Killer Cell; D007371:Interferon-gamma