Phagocytosis of apoptotic cells and cross-presentation by DC
| Project/Area Number |
22790451
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Immunology
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| Research Institution | Tohoku University |
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Principal Investigator |
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| Project Period (FY) |
2010 – 2011
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| Project Status |
Completed (Fiscal Year 2011)
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| Budget Amount *help |
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2011: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2010: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
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| Keywords | 樹状細胞 / NK細胞 / MHCクラスII / 抗原提示 / MHC class II / 細胞間膜輸送 / 貪食 / 死細胞 |
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| Research Abstract |
N atural killer (NK)cells contribute to not only innate but also 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-A b-positive when adoptively transferred into wild type (WT)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 cost imulatory 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 presentat ion. In a mouse model for delayed-type hypersensitivity, adoptive transfer of MHCII-dressed NK cells attenuated the footpad swelling. These results suggest that MHCII-dressed NK cells generated through NK-DC interactions regulate T cell-mediated immune r esponses.
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Report
(3 results)
Research Products
(21 results)
