Natural killer (NK)–dendritic cell interactions generate MHC class II-dressed NK cells that regulate CD4+ T cells

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 108; no. 45; pp. 18360 - 18365
• Main Authors: Nakayama, Masafumi, Takeda, Kazuyoshi, Kawano, Mitsuko, Takai, Toshiyuki, Ishii, Naoto, Ogasawara, Kouetsu
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 08.11.2011; National Acad Sciences
• Subjects: Adoptive transfer; Animal models; Animals; Antigen presentation; Antigen presenting cells; Binding sites; Biological Sciences; CD4 antigen; CD4-positive T-lymphocytes; CD4-Positive T-Lymphocytes - immunology; CD80 antigen; CD86 antigen; Cell interactions; Cell lines; Cell proliferation; Cells; Cellular immunity; Costimulator; Cultured cells; DAP10 protein; Dendritic cells; Dendritic Cells - immunology; Gene expression; Histocompatibility antigen HLA; Histocompatibility Antigens Class II - immunology; Humans; hypersensitivity; Hypersensitivity (delayed); Hypersensitivity, Delayed - immunology; Immune response (cell-mediated); Killer Cells, Natural - immunology; Lymphocytes T; Major histocompatibility complex; Mice; Mice, Inbred C57BL; Microscopy, Confocal; Molecules; Natural killer cells; Natural killer T cells; Physiological regulation; Plasma membranes; Proteins; Reverse Transcriptase Polymerase Chain Reaction; Rodents; Spleen; T lymphocytes
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.1110584108

Natural killer (NK) cells contribute to not only innate but also to adaptive immunity by interacting with dendritic cells (DCs) and T cells. All activated human NK cells express HLA-DR and can initiate MHCII-dependent CD4+ T-cell proliferation; however, the expression of MHCII by mouse NK cells and its functional significance are controversial. In this study, we show that NK–DC interactions result in the emergence of MHCII-positive NK cells. Upon in vitro or in vivo activation, mouse conventional NK cells did not induce MHCII transcripts, but rapidly acquired MHCII protein from DCs. MHCII H2-Ab1–deficient NK cells turned I-Ab-positive when adoptively transferred into wild-type mice or when cultured with WT splenic DCs. NK acquisition of MHCII was mediated by intercellular membrane transfer called "trogocytosis," but not upon DAP10/12- and MHCI-binding NK cell receptor signaling. MHCII-dressed NK cells concurrently acquired costimulatory molecules such as CD80 and CD86 from DCs; however, their expression did not reach functional levels. Therefore, MHCII-dressed NK cells inhibited DC-induced CD4+ T-cell responses rather than activated CD4+ T cells by competitive antigen presentation. In a mouse model for delayed-type hypersensitivity, adoptive transfer of MHCII-dressed NK cells attenuated footpad swelling. These results suggest that MHCII-dressed NK cells generated through NK–DC interactions regulate T cell-mediated immune responses.