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Memory NK cells also showed impaired activation compared with naive cells when challenged with a mutant MCMV lacking m157, highlighting their antigen-specific response. Ex vivo, MCMV-memory NK cells displayed reduced phosphorylation of STAT4 and STAT1 in response to stimulation by IL-12 and type I interferon (IFN), respectively, and IFN-\u03b3 production was reduced in response to IL-12 + IL-18 compared with naive NK cells. However, costimulation of MCMV-memory NK cells with IL-12 and m157 antigen rescues their impaired response compared with cytokines alone. These findings reveal that MCMV-primed memory NK cells are diminished in their response to cytokine-driven bystander responses to heterologous infections as they become specialized and antigen-specific for the control of MCMV upon rechallenge.<\/jats:p>","DOI":"10.1084\/jem.20141172","type":"journal-article","created":{"date-parts":[[2014,11,25]],"date-time":"2014-11-25T03:25:00Z","timestamp":1416885900000},"page":"2669-2680","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":104,"title":["Cytomegalovirus generates long-lived antigen-specific NK cells with diminished bystander activation to heterologous infection"],"prefix":"10.1084","volume":"211","author":[{"given":"Gundula","family":"Min-Oo","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology 1 and 2"},{"name":"Cancer Research Institute, University of California San Francisco, San Francisco, CA 94143 1 and 2"},{"name":"Department of Microbiology and Immunology 1 and 2"},{"name":"Cancer Research Institute, University of California San Francisco, San Francisco, CA 94143 1 and 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lewis L.","family":"Lanier","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology 1 and 2"},{"name":"Cancer Research Institute, University of California San Francisco, San Francisco, CA 94143 1 and 2"},{"name":"Department of Microbiology and Immunology 1 and 2"},{"name":"Cancer Research Institute, University of California San Francisco, San Francisco, CA 94143 1 and 2"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2014,11,24]]},"reference":[{"key":"2023072602113486400_bib1","doi-asserted-by":"publisher","first-page":"e13099","DOI":"10.1371\/journal.pone.0013099","article-title":"Role of host immune response and viral load in the differential outcome of pandemic H1N1 (2009) influenza virus infection in Indian patients","volume":"5","author":"Arankalle","year":"2010","journal-title":"PLoS ONE."},{"key":"2023072602113486400_bib2","doi-asserted-by":"publisher","first-page":"1323","DOI":"10.1126\/science.1070884","article-title":"Direct recognition of cytomegalovirus by activating and inhibitory NK cell receptors","volume":"296","author":"Arase","year":"2002","journal-title":"Science."},{"key":"2023072602113486400_bib3","first-page":"1","article-title":"Influenza: propagation, quantification, and storage","volume":"Chapter 15","author":"Balish","year":"2013","journal-title":"Curr. 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