{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T17:29:40Z","timestamp":1791221380511,"version":"4.1.0"},"reference-count":50,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2004,12,1]],"date-time":"2004-12-01T00:00:00Z","timestamp":1101859200000},"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":[[2004,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Virus-specific T cells represent a hallmark of Ag-specific, adaptive immunity. However, some T cells also demonstrate innate functions, including non-Ag-specific IFN-\u03b3 production in response to microbial products such as LPS or exposure to IL-12 and\/or IL-18. In these studies we examined LPS-induced cytokine responses of CD8+ T cells directly ex vivo. Following acute viral infection, 70\u201380% of virus-specific T cells will produce IFN-\u03b3 after exposure to LPS-induced cytokines, and neutralization experiments indicate that this is mediated almost entirely through production of IL-12 and IL-18. Different combinations of these cytokines revealed that IL-12 decreases the threshold of T cell activation by IL-18, presenting a new perspective on IL-12\/IL-18 synergy. Moreover, memory T cells demonstrate high IL-18R expression and respond effectively to the combination of IL-12 and IL-18, but cannot respond to IL-18 alone, even at high cytokine concentrations. This demonstrates that the synergy between IL-12 and IL-18 in triggering IFN-\u03b3 production by memory T cells is not simply due to up-regulation of the surface receptor for IL-18, as shown previously with naive T cells. Together, these studies indicate how virus-specific T cells are able to bridge the gap between innate and adaptive immunity during unrelated microbial infections, while attempting to protect the host from cytokine-induced immunopathology and endotoxic shock.<\/jats:p>","DOI":"10.4049\/jimmunol.173.11.6873","type":"journal-article","created":{"date-parts":[[2014,4,22]],"date-time":"2014-04-22T04:54:49Z","timestamp":1398142489000},"page":"6873-6881","source":"Crossref","is-referenced-by-count":89,"title":["Activation of Virus-Specific CD8+ T Cells by Lipopolysaccharide-Induced IL-12 and IL-18"],"prefix":"10.1093","volume":"173","author":[{"given":"Hans-Peter","family":"Raue\u0301","sequence":"first","affiliation":[{"name":"Vaccine and Gene Therapy Institute, Oregon Health and Science University , Beaverton, OR 97006"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James D","family":"Brien","sequence":"additional","affiliation":[{"name":"Vaccine and Gene Therapy Institute, Oregon Health and Science University , Beaverton, OR 97006"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erika","family":"Hammarlund","sequence":"additional","affiliation":[{"name":"Vaccine and Gene Therapy Institute, Oregon Health and Science University , Beaverton, OR 97006"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark K","family":"Slifka","sequence":"additional","affiliation":[{"name":"Vaccine and Gene Therapy Institute, Oregon Health and Science University , Beaverton, OR 97006"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2004,12,1]]},"reference":[{"key":"2025032707164960800_R1","first-page":"88","volume-title":"Nature","year":"1995"},{"key":"2025032707164960800_R2","first-page":"251","volume-title":"Annu. 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