{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T18:32:17Z","timestamp":1791311537289,"version":"4.3.1"},"reference-count":0,"publisher":"National Academy of Sciences","issue":"8","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[1993,4,15]]},"abstract":"<jats:p>Listeriosis in mice with the severe combined immunodeficiency (SCID) mutation is an established model in vivo and in vitro of interferon gamma (IFN-gamma)-dependent macrophage activation by natural killer (NK) cells during the development of natural immunity. We demonstrate that IFN-gamma production from SCID splenocytes is stimulated by interleukin (IL) 12, tumor necrosis factor alpha (TNF-alpha), and IL-2 but is inhibited by IL-10, IL-10, IL-12, and TNF are induced by heat-killed Listeria monocytogenes (hk-LM) from SCID splenocytes and peritoneal macrophages. IL-12 production is necessary for hk-LM to stimulate IFN-gamma production by SCID splenocytes since neutralization of IL-12 totally blocks IFN-gamma production in this system. TNF-alpha and IL-2 act synergistically with IL-12 to augment IFN-gamma production. Also, exogenous IL-2 increases the response of NK cells to hk-LM or to IL-12 and TNF-alpha. In contrast, IL-10 inhibits hk-LM-induced IFN-gamma production at two levels: (i) by inhibiting TNF and IL-12 production from these cultures (presumably from the macrophage) and (ii) by inhibiting the stimulatory effects of IL-12 and TNF-alpha on NK-cell IFN-gamma production. Thus, these data indicate that macrophage production of TNF-alpha and IL-12 stimulates the release of IFN-gamma by NK cells and that IL-10 produced in response to hk-LM inhibits this response at the level of the macrophage and the NK cell.<\/jats:p>","DOI":"10.1073\/pnas.90.8.3725","type":"journal-article","created":{"date-parts":[[2006,5,31]],"date-time":"2006-05-31T08:43:27Z","timestamp":1149065007000},"page":"3725-3729","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":516,"title":["Interleukin 12 and tumor necrosis factor alpha are costimulators of interferon gamma production by natural killer cells in severe combined immunodeficiency mice with listeriosis, and interleukin 10 is a physiologic antagonist."],"prefix":"10.1073","volume":"90","author":[{"given":"C S","family":"Tripp","sequence":"first","affiliation":[{"name":"Department of Pathology, Washington University School of Medicine, St. Louis, MO 63110."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S F","family":"Wolf","sequence":"additional","affiliation":[{"name":"Department of Pathology, Washington University School of Medicine, St. Louis, MO 63110."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E R","family":"Unanue","sequence":"additional","affiliation":[{"name":"Department of Pathology, Washington University School of Medicine, St. Louis, MO 63110."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[1993,4,15]]},"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.90.8.3725","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,13]],"date-time":"2022-04-13T13:27:47Z","timestamp":1649856467000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.90.8.3725"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1993,4,15]]},"references-count":0,"journal-issue":{"issue":"8","published-print":{"date-parts":[[1993,4,15]]}},"alternative-id":["10.1073\/pnas.90.8.3725"],"URL":"https:\/\/doi.org\/10.1073\/pnas.90.8.3725","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[1993,4,15]]},"assertion":[{"value":"1993-04-15","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}