{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T05:43:30Z","timestamp":1791265410024,"version":"4.1.0"},"reference-count":56,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2014,4,1]],"date-time":"2014-04-01T00:00:00Z","timestamp":1396310400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2014,4,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>NK cells are key regulators of innate defense against mouse CMV (MCMV). Like NK cells, NKT cells also produce high levels of IFN-\u03b3 rapidly after MCMV infection. However, whether similar mechanisms govern activation of these two cell types, as well as the significance of NKT cells for host resistance, remain unknown. In this article, we show that, although both NKT and NK cells are activated via cytokines, their particular cytokine requirements differ significantly in vitro and in vivo. IL-12 is required for NKT cell activation in vitro but is not sufficient, whereas NK cells have the capacity to be activated more promiscuously in response to individual cytokines from innate cells. In line with these results, GM-CSF\u2013derived dendritic cells activated only NK cells upon MCMV infection, consistent with their virtual lack of IL-12 production, whereas Flt3 ligand\u2013derived dendritic cells produced IL-12 and activated both NK and NKT cells. In vivo, NKT cell activation was abolished in IL-12\u2212\/\u2212 mice infected with MCMV, whereas NK cells were still activated. In turn, splenic NK cell activation was more IL-18 dependent. The differential requirements for IL-12 and IL-18 correlated with the levels of cytokine receptor expression by NK and NKT cells. Finally, mice lacking NKT cells showed reduced control of MCMV, and depleting NK cells further enhanced viral replication. Taken together, our results show that NKT and NK cells have differing requirements for cytokine-mediated activation, and both can contribute nonredundantly to MCMV defense, revealing that these two innate lymphocyte subsets function together to fine-tune antiviral responses.<\/jats:p>","DOI":"10.4049\/jimmunol.1300837","type":"journal-article","created":{"date-parts":[[2014,3,15]],"date-time":"2014-03-15T00:50:51Z","timestamp":1394844651000},"page":"3676-3685","source":"Crossref","is-referenced-by-count":63,"title":["Distinct Requirements for Activation of NKT and NK Cells during Viral Infection"],"prefix":"10.1093","volume":"192","author":[{"given":"Aaron J","family":"Tyznik","sequence":"first","affiliation":[{"name":"Division of Developmental Immunology, La Jolla Institute for Allergy and Immunology , La Jolla, CA 92037"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shilpi","family":"Verma","sequence":"additional","affiliation":[{"name":"Division of Immune Regulation, La Jolla Institute for Allergy and Immunology , La Jolla, CA 92037"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiao","family":"Wang","sequence":"additional","affiliation":[{"name":"Division of Immune Regulation, La Jolla Institute for Allergy and Immunology , La Jolla, CA 92037"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitchell","family":"Kronenberg","sequence":"additional","affiliation":[{"name":"Division of Developmental Immunology, La Jolla Institute for Allergy and Immunology , La Jolla, CA 92037"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chris A","family":"Benedict","sequence":"additional","affiliation":[{"name":"Division of Immune Regulation, La Jolla Institute for Allergy and Immunology , La Jolla, CA 92037"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2014,4,15]]},"reference":[{"key":"2025032404230326400_r1","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1111\/j.1365-2796.2010.02220.x","article-title":"Modulation of host innate and adaptive immune defenses by cytomegalovirus: timing is everything","volume":"267","author":"Loewendorf","year":"2010","journal-title":"J. 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