{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T17:06:27Z","timestamp":1791219987906,"version":"4.1.0"},"reference-count":51,"publisher":"Elsevier BV","issue":"2","license":[{"start":{"date-parts":[[2013,2,1]],"date-time":"2013-02-01T00:00:00Z","timestamp":1359676800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2014,2,21]],"date-time":"2014-02-21T00:00:00Z","timestamp":1392940800000},"content-version":"vor","delay-in-days":385,"URL":"https:\/\/www.elsevier.com\/open-access\/userlicense\/1.0\/"}],"content-domain":{"domain":["cell.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Immunity"],"published-print":{"date-parts":[[2013,2]]},"DOI":"10.1016\/j.immuni.2012.10.022","type":"journal-article","created":{"date-parts":[[2013,2,21]],"date-time":"2013-02-21T15:08:39Z","timestamp":1361459319000},"page":"309-321","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":128,"title":["Chronic but Not Acute Virus Infection Induces Sustained Expansion of Myeloid Suppressor Cell Numbers that Inhibit Viral-Specific T Cell Immunity"],"prefix":"10.1016","volume":"38","author":[{"given":"Brian\u00a0A.","family":"Norris","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luke\u00a0S.","family":"Uebelhoer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helder\u00a0I.","family":"Nakaya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aryn\u00a0A.","family":"Price","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arash","family":"Grakoui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bali","family":"Pulendran","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.immuni.2012.10.022_bib1","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1084\/jem.160.2.521","article-title":"Selection of genetic variants of lymphocytic choriomeningitis virus in spleens of persistently infected mice. Role in suppression of cytotoxic T lymphocyte response and viral persistence","volume":"160","author":"Ahmed","year":"1984","journal-title":"J.\u00a0Exp. Med."},{"key":"10.1016\/j.immuni.2012.10.022_bib2","doi-asserted-by":"crossref","first-page":"3301","DOI":"10.1128\/JVI.62.9.3301-3308.1988","article-title":"Genetic analysis of in\u00a0vivo-selected viral variants causing chronic infection: importance of mutation in the L RNA segment of lymphocytic choriomeningitis virus","volume":"62","author":"Ahmed","year":"1988","journal-title":"J.\u00a0Virol."},{"key":"10.1016\/j.immuni.2012.10.022_bib3","doi-asserted-by":"crossref","first-page":"1144","DOI":"10.1038\/ni736","article-title":"Mouse type I IFN-producing cells are immature APCs with plasmacytoid morphology","volume":"2","author":"Asselin-Paturel","year":"2001","journal-title":"Nat. Immunol."},{"key":"10.1016\/j.immuni.2012.10.022_bib4","doi-asserted-by":"crossref","first-page":"682","DOI":"10.1038\/nature04444","article-title":"Restoring function in exhausted CD8 T\u00a0cells during chronic viral infection","volume":"439","author":"Barber","year":"2006","journal-title":"Nature"},{"key":"10.1016\/j.immuni.2012.10.022_bib5","doi-asserted-by":"crossref","first-page":"21641","DOI":"10.1073\/pnas.1011998107","article-title":"Viral replicative capacity is the primary determinant of lymphocytic choriomeningitis virus persistence and immunosuppression","volume":"107","author":"Bergthaler","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.immuni.2012.10.022_bib6","doi-asserted-by":"crossref","first-page":"1059","DOI":"10.1128\/JVI.69.2.1059-1070.1995","article-title":"Virus-induced immunosuppression: immune system-mediated destruction of virus-infected dendritic cells results in generalized immune suppression","volume":"69","author":"Borrow","year":"1995","journal-title":"J.\u00a0Virol."},{"key":"10.1016\/j.immuni.2012.10.022_bib7","doi-asserted-by":"crossref","first-page":"1301","DOI":"10.1038\/nm1492","article-title":"Interleukin-10 determines viral clearance or persistence in\u00a0vivo","volume":"12","author":"Brooks","year":"2006","journal-title":"Nat. Med."},{"key":"10.1016\/j.immuni.2012.10.022_bib8","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/S1074-7613(00)80469-0","article-title":"Massive expansion of antigen-specific CD8+ T\u00a0cells during an acute virus infection","volume":"8","author":"Butz","year":"1998","journal-title":"Immunity"},{"key":"10.1016\/j.immuni.2012.10.022_bib9","doi-asserted-by":"crossref","first-page":"336","DOI":"10.1038\/nri1349","article-title":"Co-inhibitory molecules of the B7-CD28 family in the control of T-cell immunity","volume":"4","author":"Chen","year":"2004","journal-title":"Nat. Rev. Immunol."},{"key":"10.1016\/j.immuni.2012.10.022_bib10","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1189\/jlb.0407247","article-title":"Use of Ly6G-specific monoclonal antibody to deplete neutrophils in mice","volume":"83","author":"Daley","year":"2008","journal-title":"J.\u00a0Leukoc. Biol."},{"key":"10.1016\/j.immuni.2012.10.022_bib11","doi-asserted-by":"crossref","first-page":"1463","DOI":"10.1084\/jem.20062602","article-title":"MyD88-dependent expansion of an immature GR-1(+)CD11b(+) population induces T\u00a0cell suppression and Th2 polarization in sepsis","volume":"204","author":"Delano","year":"2007","journal-title":"J.\u00a0Exp. Med."},{"key":"10.1016\/j.immuni.2012.10.022_bib12","doi-asserted-by":"crossref","first-page":"1685","DOI":"10.1084\/jem.192.12.1685","article-title":"CD8(+) but not CD8(-) dendritic cells cross-prime cytotoxic T\u00a0cells in\u00a0vivo","volume":"192","author":"den Haan","year":"2000","journal-title":"J.\u00a0Exp. Med."},{"key":"10.1016\/j.immuni.2012.10.022_bib13","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1038\/nature01783","article-title":"Viral infection switches non-plasmacytoid dendritic cells into high interferon producers","volume":"424","author":"Diebold","year":"2003","journal-title":"Nature"},{"key":"10.1016\/j.immuni.2012.10.022_bib14","doi-asserted-by":"crossref","first-page":"916","DOI":"10.1172\/JCI27203","article-title":"Yeast zymosan, a stimulus for TLR2 and dectin-1, induces regulatory antigen-presenting cells and immunological tolerance","volume":"116","author":"Dillon","year":"2006","journal-title":"J.\u00a0Clin. Invest."},{"key":"10.1016\/j.immuni.2012.10.022_bib15","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1038\/nri2506","article-title":"Myeloid-derived suppressor cells as regulators of the immune system","volume":"9","author":"Gabrilovich","year":"2009","journal-title":"Nat. Rev. Immunol."},{"key":"10.1016\/j.immuni.2012.10.022_bib16","doi-asserted-by":"crossref","first-page":"2777","DOI":"10.1172\/JCI28828","article-title":"Tumors induce a subset of inflammatory monocytes with immunosuppressive activity on CD8+ T\u00a0cells","volume":"116","author":"Gallina","year":"2006","journal-title":"J.\u00a0Clin. Invest."},{"key":"10.1016\/j.immuni.2012.10.022_bib17","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/S1074-7613(03)00174-2","article-title":"Blood monocytes consist of two principal subsets with distinct migratory properties","volume":"19","author":"Geissmann","year":"2003","journal-title":"Immunity"},{"key":"10.1016\/j.immuni.2012.10.022_bib18","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/j.immuni.2005.01.005","article-title":"Viruses evade the immune system through type I interferon-mediated STAT2-dependent, but STAT1-independent, signaling","volume":"22","author":"Hahm","year":"2005","journal-title":"Immunity"},{"key":"10.1016\/j.immuni.2012.10.022_bib19","doi-asserted-by":"crossref","first-page":"1123","DOI":"10.1158\/0008-5472.CAN-05-1299","article-title":"Gr-1+CD115+ immature myeloid suppressor cells mediate the development of tumor-induced T regulatory cells and T-cell anergy in tumor-bearing host","volume":"66","author":"Huang","year":"2006","journal-title":"Cancer Res."},{"key":"10.1016\/j.immuni.2012.10.022_bib20","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1016\/j.canlet.2006.12.012","article-title":"CCL2\/CCR2 pathway mediates recruitment of myeloid suppressor cells to cancers","volume":"252","author":"Huang","year":"2007","journal-title":"Cancer Lett."},{"key":"10.1016\/j.immuni.2012.10.022_bib21","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1128\/JVI.01640-07","article-title":"Lymphocytoid choriomeningitis virus activates plasmacytoid dendritic cells and induces a cytotoxic T-cell response via MyD88","volume":"82","author":"Jung","year":"2008","journal-title":"J.\u00a0Virol."},{"key":"10.1016\/j.immuni.2012.10.022_bib22","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1038\/nature07591","article-title":"Myelomonocytic cell recruitment causes fatal CNS vascular injury during acute viral meningitis","volume":"457","author":"Kim","year":"2009","journal-title":"Nature"},{"key":"10.1016\/j.immuni.2012.10.022_bib23","doi-asserted-by":"crossref","first-page":"873","DOI":"10.1038\/ni1241","article-title":"T cells and viral persistence: lessons from diverse infections","volume":"6","author":"Klenerman","year":"2005","journal-title":"Nat. Immunol."},{"key":"10.1016\/j.immuni.2012.10.022_bib24","doi-asserted-by":"crossref","first-page":"989","DOI":"10.4049\/jimmunol.172.2.989","article-title":"Antigen-specific inhibition of CD8+ T\u00a0cell response by immature myeloid cells in cancer is mediated by reactive oxygen species","volume":"172","author":"Kusmartsev","year":"2004","journal-title":"J.\u00a0Immunol."},{"key":"10.1016\/j.immuni.2012.10.022_bib25","doi-asserted-by":"crossref","first-page":"876","DOI":"10.1158\/0008-5472.CAN-11-1792","article-title":"Monocytic CCR2(+) myeloid-derived suppressor cells promote immune escape by limiting activated CD8 T-cell infiltration into the tumor microenvironment","volume":"72","author":"Lesokhin","year":"2012","journal-title":"Cancer Res."},{"key":"10.1016\/j.immuni.2012.10.022_bib26","doi-asserted-by":"crossref","first-page":"9192","DOI":"10.1128\/JVI.00555-06","article-title":"Inhibition of the type I interferon response by the nucleoprotein of the prototypic arenavirus lymphocytic choriomeningitis virus","volume":"80","author":"Mart\u00ednez-Sobrido","year":"2006","journal-title":"J.\u00a0Virol."},{"key":"10.1016\/j.immuni.2012.10.022_bib27","doi-asserted-by":"crossref","first-page":"7340","DOI":"10.1128\/JVI.67.12.7340-7349.1993","article-title":"Molecular determinants of macrophage tropism and viral persistence: importance of single amino acid changes in the polymerase and glycoprotein of lymphocytic choriomeningitis virus","volume":"67","author":"Matloubian","year":"1993","journal-title":"J.\u00a0Virol."},{"key":"10.1016\/j.immuni.2012.10.022_bib28","doi-asserted-by":"crossref","first-page":"936","DOI":"10.1126\/science.1214935","article-title":"Disease tolerance as a defense strategy","volume":"335","author":"Medzhitov","year":"2012","journal-title":"Science"},{"key":"10.1016\/j.immuni.2012.10.022_bib29","doi-asserted-by":"crossref","first-page":"8128","DOI":"10.1016\/S0021-9258(17)37169-7","article-title":"Regulation of nitric-oxide synthase mRNA expression by interferon-gamma and picolinic acid","volume":"269","author":"Melillo","year":"1994","journal-title":"J.\u00a0Biol. Chem."},{"key":"10.1016\/j.immuni.2012.10.022_bib30","doi-asserted-by":"crossref","first-page":"1851","DOI":"10.4049\/jimmunol.174.4.1851","article-title":"Rapid activation of spleen dendritic cell subsets following lymphocytic choriomeningitis virus infection of mice: analysis of the involvement of type 1 IFN","volume":"174","author":"Montoya","year":"2005","journal-title":"J.\u00a0Immunol."},{"key":"10.1016\/j.immuni.2012.10.022_bib31","doi-asserted-by":"crossref","first-page":"8623","DOI":"10.1073\/pnas.0809818106","article-title":"High antigen levels are the cause of T\u00a0cell exhaustion during chronic viral infection","volume":"106","author":"Mueller","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.immuni.2012.10.022_bib32","doi-asserted-by":"crossref","first-page":"15430","DOI":"10.1073\/pnas.0702579104","article-title":"Viral targeting of fibroblastic reticular cells contributes to immunosuppression and persistence during chronic infection","volume":"104","author":"Mueller","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.immuni.2012.10.022_bib33","doi-asserted-by":"crossref","first-page":"8252","DOI":"10.1073\/pnas.88.18.8252","article-title":"Virus-triggered acquired immunodeficiency by cytotoxic T-cell-dependent destruction of antigen-presenting cells and lymph follicle structure","volume":"88","author":"Odermatt","year":"1991","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.immuni.2012.10.022_bib34","doi-asserted-by":"crossref","first-page":"1036","DOI":"10.1073\/pnas.96.3.1036","article-title":"Distinct dendritic cell subsets differentially regulate the class of immune response in\u00a0vivo","volume":"96","author":"Pulendran","year":"1999","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.immuni.2012.10.022_bib35","doi-asserted-by":"crossref","first-page":"3538","DOI":"10.1002\/eji.200939530","article-title":"Gr-1 antibody induces STAT signaling, macrophage marker expression and abrogation of myeloid-derived suppressor cell activity in BM cells","volume":"39","author":"Ribechini","year":"2009","journal-title":"Eur. J. Immunol."},{"key":"10.1016\/j.immuni.2012.10.022_bib36","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1038\/ni1309","article-title":"Monocyte emigration from bone marrow during bacterial infection requires signals mediated by chemokine receptor CCR2","volume":"7","author":"Serbina","year":"2006","journal-title":"Nat. Immunol."},{"key":"10.1016\/j.immuni.2012.10.022_bib37","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1146\/annurev.immunol.26.021607.090326","article-title":"Monocyte-mediated defense against microbial pathogens","volume":"26","author":"Serbina","year":"2008","journal-title":"Annu. Rev. Immunol."},{"key":"10.1016\/j.immuni.2012.10.022_bib38","doi-asserted-by":"crossref","first-page":"1249","DOI":"10.1084\/jem.192.9.1249","article-title":"Immunosuppression and resultant viral persistence by specific viral targeting of dendritic cells","volume":"192","author":"Sevilla","year":"2000","journal-title":"J.\u00a0Exp. Med."},{"key":"10.1016\/j.immuni.2012.10.022_bib39","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1172\/JCI20243","article-title":"Viral targeting of hematopoietic progenitors and inhibition of DC maturation as a dual strategy for immune subversion","volume":"113","author":"Sevilla","year":"2004","journal-title":"J.\u00a0Clin. Invest."},{"key":"10.1016\/j.immuni.2012.10.022_bib40","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1038\/nri727","article-title":"The B7-CD28 superfamily","volume":"2","author":"Sharpe","year":"2002","journal-title":"Nat. Rev. Immunol."},{"key":"10.1016\/j.immuni.2012.10.022_bib41","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1128\/JVI.75.1.448-457.2001","article-title":"Differences in affinity of binding of lymphocytic choriomeningitis virus strains to the cellular receptor alpha-dystroglycan correlate with viral tropism and disease kinetics","volume":"75","author":"Smelt","year":"2001","journal-title":"J.\u00a0Virol."},{"key":"10.1016\/j.immuni.2012.10.022_bib42","doi-asserted-by":"crossref","first-page":"1746","DOI":"10.4049\/jimmunol.177.3.1746","article-title":"Innate inflammatory signals induced by various pathogens differentially dictate the IFN-I dependence of CD8 T\u00a0cells for clonal expansion and memory formation","volume":"177","author":"Thompson","year":"2006","journal-title":"J.\u00a0Immunol."},{"key":"10.1016\/j.immuni.2012.10.022_bib43","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/j.immuni.2009.06.015","article-title":"Cell-intrinsic transforming growth factor-beta signaling mediates virus-specific CD8+ T\u00a0cell deletion and viral persistence in\u00a0vivo","volume":"31","author":"Tinoco","year":"2009","journal-title":"Immunity"},{"key":"10.1016\/j.immuni.2012.10.022_bib44","doi-asserted-by":"crossref","first-page":"5487","DOI":"10.1128\/IAI.72.9.5487-5492.2004","article-title":"Both expansion of regulatory GR1+ CD11b+ myeloid cells and anergy of T lymphocytes participate in hyporesponsiveness of the lung-associated immune system during acute toxoplasmosis","volume":"72","author":"Voisin","year":"2004","journal-title":"Infect. Immun."},{"key":"10.1016\/j.immuni.2012.10.022_bib45","doi-asserted-by":"crossref","first-page":"4911","DOI":"10.1128\/JVI.77.8.4911-4927.2003","article-title":"Viral persistence alters CD8 T-cell immunodominance and tissue distribution and results in distinct stages of functional impairment","volume":"77","author":"Wherry","year":"2003","journal-title":"J.\u00a0Virol."},{"key":"10.1016\/j.immuni.2012.10.022_bib46","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1038\/ni889","article-title":"Lineage relationship and protective immunity of memory CD8 T\u00a0cell subsets","volume":"4","author":"Wherry","year":"2003","journal-title":"Nat. Immunol."},{"key":"10.1016\/j.immuni.2012.10.022_bib47","doi-asserted-by":"crossref","first-page":"6807","DOI":"10.1158\/0008-5472.CAN-05-3755","article-title":"CD80 in immune suppression by mouse ovarian carcinoma-associated Gr-1+CD11b+ myeloid cells","volume":"66","author":"Yang","year":"2006","journal-title":"Cancer Res."},{"key":"10.1016\/j.immuni.2012.10.022_bib48","doi-asserted-by":"crossref","first-page":"5791","DOI":"10.4049\/jimmunol.181.8.5791","article-title":"Subsets of myeloid-derived suppressor cells in tumor-bearing mice","volume":"181","author":"Youn","year":"2008","journal-title":"J.\u00a0Immunol."},{"key":"10.1016\/j.immuni.2012.10.022_bib49","doi-asserted-by":"crossref","first-page":"2205","DOI":"10.1084\/jem.188.12.2205","article-title":"Viral immune evasion due to persistence of activated T\u00a0cells without effector function","volume":"188","author":"Zajac","year":"1998","journal-title":"J.\u00a0Exp. Med."},{"key":"10.1016\/j.immuni.2012.10.022_bib50","doi-asserted-by":"crossref","first-page":"5228","DOI":"10.4049\/jimmunol.179.8.5228","article-title":"CD11b+Ly-6C(hi) suppressive monocytes in experimental autoimmune encephalomyelitis","volume":"179","author":"Zhu","year":"2007","journal-title":"J.\u00a0Immunol."},{"key":"10.1016\/j.immuni.2012.10.022_bib51","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1016\/j.chom.2008.08.016","article-title":"Persistent virus infection inhibits type I interferon production by plasmacytoid dendritic cells to facilitate opportunistic infections","volume":"4","author":"Zuniga","year":"2008","journal-title":"Cell Host Microbe"}],"container-title":["Immunity"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1074761313000551?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1074761313000551?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2022,2,9]],"date-time":"2022-02-09T00:11:42Z","timestamp":1644365502000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1074761313000551"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,2]]},"references-count":51,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2013,2]]}},"alternative-id":["S1074761313000551"],"URL":"https:\/\/doi.org\/10.1016\/j.immuni.2012.10.022","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.717982280.793475756","asserted-by":"object"}]},"ISSN":["1074-7613"],"issn-type":[{"value":"1074-7613","type":"print"}],"subject":[],"published":{"date-parts":[[2013,2]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Chronic but Not Acute Virus Infection Induces Sustained Expansion of Myeloid Suppressor Cell Numbers that Inhibit Viral-Specific T Cell Immunity","name":"articletitle","label":"Article Title"},{"value":"Immunity","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.immuni.2012.10.022","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"Copyright \u00a9 2013 Elsevier Inc. All rights reserved.","name":"copyright","label":"Copyright"}]}}