DNAM-1 is required for expansion of effector NK cells and generation of memory NK cells during mouse cytomegalovirus infection (P6100)
| Autor: | Tsukasa Nabekura, Lewis Lanier |
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| Rok vydání: | 2013 |
| Předmět: | |
| Zdroj: | The Journal of Immunology. 190:173.5-173.5 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.190.supp.173.5 |
| Popis: | Recent studies have demonstrated that natural killer (NK) cells have adaptive immune features including antigen-specific expansion and subsequent generation of a memory subset. However, the precise signaling pathways that promote the expansion and the generation of memory NK cells remain to be elucidated. Using mixed bone marrow chimeric mice, we investigated the role of DNAM-1, an activating NK cell receptor, in expansion and memory generation of NK cells in a mouse model of cytomegalovirus infection (MCMV). We demonstrated that DNAM-1-deficient MCMV-specific Ly49H+ NK cells exhibit not only a poor expansion following MCMV infection, but also defects in both memory NK cell generation and secondary expansion after re-challenge with MCMV, as compared with wild type Ly49H+ NK cells. The frequency of DNAM-1- NK cells bearing Ly49H gradually increase and the long-lived Ly49H+ NK cells do not express DNAM-1 in MCMV-infected wild type mice. Interestingly, DNAM-1-Ly49H+ effector NK cells are more proliferative and less sensitive to cell death than DNAM-1+Ly49H+ NK cells during MCMV infection. These observations suggest that cooperative signaling through DNAM-1 and Ly49H induces downmodulation of DNAM-1 on Ly49H+ NK cells, resulting in predominant expansion and persistence of DNAM-1-Ly49H+ NK cells during MCMV infection. Therefore, DNAM-1 is a key molecule for optimal effector response and memory generation of virus-specific NK cells. |
| Databáze: | OpenAIRE |
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