{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T22:51:03Z","timestamp":1790895063577,"version":"4.1.0"},"reference-count":30,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2000,1,1]],"date-time":"2000-01-01T00:00:00Z","timestamp":946684800000},"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":[[2000,1,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Some, but not all, viral infections induce endogenous IL-12 to drive NK cell IFN-\u03b3 production and downstream antiviral defenses during innate immune responses. Even though lymphocytic choriomeningitis virus (LCMV) can be sensitive to IFN-\u03b3-mediated antiviral effects, infections with this agent do not elicit IL-12 or early IFN-\u03b3 in immunocompetent hosts. Studies presented here demonstrate that LCMV infections of mice not only fail to induce IL-12, but also modify responsiveness to exogenous IL-12 for IFN-\u03b3 production. IFN-\u03b3 responses induced by IL-12 administration were greatly diminished in splenic populations, but significantly increased in serum and hepatic leukocytes, during the early course of LCMV infections. The IFN-\u03b3 production was NK cell dependent, and the compartmental dichotomy between spleen and liver was also demonstrated in response to in vitro IL-12 stimulation. Although infections did increase proportions and numbers of liver NK cells, changes in responsiveness for IFN-\u03b3 expression could not be explained by cell redistribution. Corroborating changes in proportions of NK cells induced to express intracellular IFN-\u03b3 protein within the compartments were observed. The reduction in ability of splenic populations to produce IL-12-induced IFN-\u03b3 after infection by LCMV was associated with decreased efficacy of administered IL-12 for promoting IFN-\u03b3-dependent antiviral effects in the spleen. Concomitantly, the maintenance of hepatic population IFN-\u03b3 production was associated with preserved efficacy of administered IL-12 to elicit IFN-\u03b3-dependent antiviral effects in the liver. Taken together, these results demonstrate modifications of compartmental responses to IL-12 by viral infections and the consequences of these changes for efficacy of cytokine therapy.<\/jats:p>","DOI":"10.4049\/jimmunol.164.2.994","type":"journal-article","created":{"date-parts":[[2014,4,20]],"date-time":"2014-04-20T19:46:15Z","timestamp":1398023175000},"page":"994-1001","source":"Crossref","is-referenced-by-count":39,"title":["Compartmental Differences in NK Cell Responsiveness to IL-12 During Lymphocytic Choriomeningitis Virus Infection"],"prefix":"10.1093","volume":"164","author":[{"given":"Gary C","family":"Pien","sequence":"first","affiliation":[{"name":"Department of Molecular Microbiology and Immunology, Division of Biology and Medicine, Brown University , Providence, RI 02912"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine A","family":"Biron","sequence":"additional","affiliation":[{"name":"Department of Molecular Microbiology and Immunology, Division of Biology and Medicine, Brown University , Providence, RI 02912"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2000,1,15]]},"reference":[{"key":"2026020213190865100_R1","first-page":"251","volume-title":"Annu. 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