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Therefore, establishing the molecular signals that control whether PDL-1 stimulates immune suppression or activation is important as immune modulation therapies based on manipulating PDL-1 are being developed. In this study, the requirement for PDL-1 blockade initiated before infection with the intracellular bacterium Listeria monocytogenes in reducing pathogen-specific T cell expansion is demonstrated. In turn, the role of proinflammatory cytokines triggered early after L. monocytogenes infection in controlling PDL-1\u2013mediated T cell stimulation was investigated using mice with targeted defects in specific cytokines or cytokine receptors. These experiments illustrate an essential role for IL-12 or type I IFNs in PDL-1\u2013mediated expansion of pathogen-specific CD8+ T cells. Unexpectedly, direct stimulation by neither IL-12 nor type I IFNs on pathogen-specific CD8+ cells was essential for PDL-1\u2013mediated expansion. Instead, the absence of early innate IFN-\u03b3 production in mice with combined defects in both IL-12 and type I IFNR negated the impacts of PDL-1 blockade. In turn, IFN-\u03b3 ablation using neutralizing Abs or in mice with targeted defects in IFN-\u03b3R each eliminated the PDL-1\u2013mediated stimulatory impacts on pathogen-specific T cell expansion. Thus, innate IFN-\u03b3 is essential for PDL-1\u2013mediated T cell stimulation.<\/jats:p>","DOI":"10.4049\/jimmunol.1103227","type":"journal-article","created":{"date-parts":[[2012,6,19]],"date-time":"2012-06-19T03:47:24Z","timestamp":1340077644000},"page":"876-884","source":"Crossref","is-referenced-by-count":17,"title":["Innate IFN-\u03b3 Is Essential for Programmed Death Ligand-1\u2013Mediated T Cell Stimulation following <i>Listeria monocytogenes<\/i> Infection"],"prefix":"10.1093","volume":"189","author":[{"given":"Jared H","family":"Rowe","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Center for Microbiology and Infectious Disease Translational Research, University of Minnesota School of Medicine , Minneapolis, MN 55455; and , Minneapolis, MN 55455"},{"name":"Department of Microbiology, Center for Microbiology and Infectious Disease Translational Research, University of Minnesota School of Medicine , Minneapolis, MN 55455; and , Minneapolis, MN 55455"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James M","family":"Ertelt","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Center for Microbiology and Infectious Disease Translational Research, University of Minnesota School of Medicine , Minneapolis, MN 55455; and , Minneapolis, MN 55455"},{"name":"Department of Microbiology, Center for Microbiology and Infectious Disease Translational Research, University of Minnesota School of Medicine , Minneapolis, MN 55455; and , Minneapolis, MN 55455"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sing Sing","family":"Way","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Center for Microbiology and Infectious Disease Translational Research, University of Minnesota School of Medicine , Minneapolis, MN 55455; and , Minneapolis, MN 55455"},{"name":"Department of Microbiology, Center for Microbiology and Infectious Disease Translational Research, University of Minnesota School of Medicine , Minneapolis, MN 55455; and , Minneapolis, MN 55455"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2012,7,15]]},"reference":[{"key":"2025032409211634400_r1","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1016\/j.coi.2007.04.012","article-title":"PD-1 and its ligands in T-cell immunity","volume":"19","author":"Keir","year":"2007","journal-title":"Curr. 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