{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T06:56:28Z","timestamp":1791356188885,"version":"4.3.1"},"reference-count":38,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2014,1,1]],"date-time":"2014-01-01T00:00:00Z","timestamp":1388534400000},"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":[[2014,1,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Regulatory T cells (Tregs) are well known for their role in dampening the immune responses to self-Ags and, thereby, limiting autoimmunity. However, they also must permit immune responses to occur against foreign infectious agents. Using a mouse model of West Nile virus infection, we examined the role of Tregs in the generation of effector and memory T cell responses in the secondary lymphoid organs, as well as the infected tissues. We found that Treg numbers and activation increased in both the secondary lymphoid organs and CNS postinfection. Using Foxp3DTR knock-in mice, we found that Treg-deficient mice had increased Ag-driven production of IFN-\u03b3 from both CD4+ and CD8+ T cells in the spleen and CNS during the effector phase. In mice lacking Tregs, there were greater numbers of short-lived effector CD8+ T cells in the spleen during the peak of the immune response, but the memory CD8+ T cell response was impaired. Specifically, we demonstrate that Treg-dependent production of TGF-\u03b2 results in increased expression of CD103 on CD8+ T cells, thereby allowing for a large pool of resident memory T cells to be maintained in the brain postinfection.<\/jats:p>","DOI":"10.4049\/jimmunol.1202153","type":"journal-article","created":{"date-parts":[[2013,12,11]],"date-time":"2013-12-11T22:26:31Z","timestamp":1386800791000},"page":"683-690","source":"Crossref","is-referenced-by-count":102,"title":["Regulatory T Cells Shape the Resident Memory T Cell Response to Virus Infection in the Tissues"],"prefix":"10.1093","volume":"192","author":[{"given":"Jessica B","family":"Graham","sequence":"first","affiliation":[{"name":"Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center , Seattle, WA 98109"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreia","family":"Da Costa","sequence":"additional","affiliation":[{"name":"Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center , Seattle, WA 98109"},{"name":"Graduate Program in Pathobiology, Department of Global Health, University of Washington , Seattle, WA 98195"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer M","family":"Lund","sequence":"additional","affiliation":[{"name":"Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center , Seattle, WA 98109"},{"name":"Graduate Program in Pathobiology, Department of Global Health, University of Washington , Seattle, WA 98195"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2014,1,15]]},"reference":[{"key":"2025032404080547500_r1","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1038\/nri2916","article-title":"Phenotypical and functional specialization of FOXP3+ regulatory T cells","volume":"11","author":"Campbell","year":"2011","journal-title":"Nat. Rev. Immunol."},{"key":"2025032404080547500_r2","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1146\/annurev.immunol.25.022106.141623","article-title":"Regulatory T cells: mechanisms of differentiation and function","volume":"30","author":"Josefowicz","year":"2012","journal-title":"Annu. Rev. Immunol."},{"key":"2025032404080547500_r3","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1146\/annurev.immunol.021908.132723","article-title":"Regulatory T cells in the control of host-microorganism interactions (*)","volume":"27","author":"Belkaid","year":"2009","journal-title":"Annu. Rev. Immunol."},{"key":"2025032404080547500_r4","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1038\/ni1181","article-title":"Natural regulatory T cells in infectious disease","volume":"6","author":"Belkaid","year":"2005","journal-title":"Nat. Immunol."},{"key":"2025032404080547500_r5","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1038\/nature01152","article-title":"CD4+CD25+ regulatory T cells control Leishmania major persistence and immunity","volume":"420","author":"Belkaid","year":"2002","journal-title":"Nature"},{"key":"2025032404080547500_r6","doi-asserted-by":"crossref","first-page":"1220","DOI":"10.1126\/science.1155209","article-title":"Coordination of early protective immunity to viral infection by regulatory T cells","volume":"320","author":"Lund","year":"2008","journal-title":"Science"},{"key":"2025032404080547500_r7","doi-asserted-by":"crossref","first-page":"3024","DOI":"10.2741\/3432","article-title":"The host immunologic response to West Nile encephalitis virus","volume":"14","author":"Diamond","year":"2009","journal-title":"Front. Biosci. (Landmark Ed.)"},{"key":"2025032404080547500_r8","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1093\/jb\/mvm032","article-title":"Antiviral signaling through pattern recognition receptors","volume":"141","author":"Kawai","year":"2007","journal-title":"J. Biochem."},{"key":"2025032404080547500_r9","doi-asserted-by":"crossref","first-page":"2578","DOI":"10.1128\/JVI.77.4.2578-2586.2003","article-title":"B cells and antibody play critical roles in the immediate defense of disseminated infection by West Nile encephalitis virus","volume":"77","author":"Diamond","year":"2003","journal-title":"J. Virol."},{"key":"2025032404080547500_r10","doi-asserted-by":"crossref","first-page":"1853","DOI":"10.1084\/jem.20031223","article-title":"A critical role for induced IgM in the protection against West Nile virus infection","volume":"198","author":"Diamond","year":"2003","journal-title":"J. Exp. Med."},{"key":"2025032404080547500_r11","doi-asserted-by":"crossref","first-page":"3599","DOI":"10.1099\/vir.0.81306-0","article-title":"CD8(+) T cell-mediated immune responses in West Nile virus (Sarafend strain) encephalitis are independent of gamma interferon","volume":"87","author":"Wang","year":"2006","journal-title":"J. Gen. Virol."},{"key":"2025032404080547500_r12","doi-asserted-by":"crossref","first-page":"12060","DOI":"10.1128\/JVI.01650-06","article-title":"CD4+ T-cell responses are required for clearance of West Nile virus from the central nervous system","volume":"80","author":"Sitati","year":"2006","journal-title":"J. Virol."},{"key":"2025032404080547500_r13","doi-asserted-by":"crossref","first-page":"17140","DOI":"10.1073\/pnas.0705837104","article-title":"Axonal transport mediates West Nile virus entry into the central nervous system and induces acute flaccid paralysis","volume":"104","author":"Samuel","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2025032404080547500_r14","doi-asserted-by":"crossref","first-page":"2524","DOI":"10.4049\/jimmunol.171.5.2524","article-title":"IFN-gamma-producing gamma delta T cells help control murine West Nile virus infection","volume":"171","author":"Wang","year":"2003","journal-title":"J. Immunol."},{"key":"2025032404080547500_r15","doi-asserted-by":"crossref","first-page":"8312","DOI":"10.1128\/JVI.78.15.8312-8321.2004","article-title":"Role of CD8+ T cells in control of West Nile virus infection","volume":"78","author":"Shrestha","year":"2004","journal-title":"J. Virol."},{"key":"2025032404080547500_r16","doi-asserted-by":"crossref","first-page":"1087","DOI":"10.1084\/jem.20042530","article-title":"Chemokine receptor CCR5 promotes leukocyte trafficking to the brain and survival in West Nile virus infection","volume":"202","author":"Glass","year":"2005","journal-title":"J. Exp. Med."},{"key":"2025032404080547500_r17","doi-asserted-by":"crossref","first-page":"11457","DOI":"10.1128\/JVI.79.17.11457-11466.2005","article-title":"Neuronal CXCL10 directs CD8+ T-cell recruitment and control of West Nile virus encephalitis","volume":"79","author":"Klein","year":"2005","journal-title":"J. Virol."},{"key":"2025032404080547500_r18","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1002\/jmv.20205","article-title":"Different chemokine expression in lethal and non-lethal murine West Nile virus infection","volume":"74","author":"Shirato","year":"2004","journal-title":"J. Med. Virol."},{"key":"2025032404080547500_r19","doi-asserted-by":"crossref","first-page":"e10649","DOI":"10.1371\/journal.pone.0010649","article-title":"Persistence of West Nile virus in the central nervous system and periphery of mice","volume":"5","author":"Appler","year":"2010","journal-title":"PLoS ONE"},{"key":"2025032404080547500_r20","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1186\/1471-2172-12-6","article-title":"Persistence of virus-specific immune responses in the central nervous system of mice after West Nile virus infection","volume":"12","author":"Stewart","year":"2011","journal-title":"BMC Immunol."},{"key":"2025032404080547500_r21","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1080\/13550280601187185","article-title":"West Nile virus encephalitis: sequential histopathological and immunological events in a murine model of infection","volume":"13","author":"Garcia-Tapia","year":"2007","journal-title":"J. Neurovirol."},{"key":"2025032404080547500_r22","first-page":"3266","article-title":"Tregs control the development of symptomatic West Nile virus infection in humans and mice","volume":"119","author":"Lanteri","year":"2009","journal-title":"J. Clin. Invest."},{"key":"2025032404080547500_r23","doi-asserted-by":"crossref","first-page":"9424","DOI":"10.1128\/JVI.00768-06","article-title":"Resistance to alpha\/beta interferon is a determinant of West Nile virus replication fitness and virulence","volume":"80","author":"Keller","year":"2006","journal-title":"J. Virol."},{"key":"2025032404080547500_r24","doi-asserted-by":"crossref","first-page":"e1000757","DOI":"10.1371\/journal.ppat.1000757","article-title":"IPS-1 is essential for the control of West Nile virus infection and immunity","volume":"6","author":"Suthar","year":"2010","journal-title":"PLoS Pathog."},{"key":"2025032404080547500_r25","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1038\/ni1428","article-title":"Regulatory T cells prevent catastrophic autoimmunity throughout the lifespan of mice","volume":"8","author":"Kim","year":"2007","journal-title":"Nat. Immunol."},{"key":"2025032404080547500_r26","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1016\/j.immuni.2005.01.016","article-title":"Regulatory T cell lineage specification by the forkhead transcription factor foxp3","volume":"22","author":"Fontenot","year":"2005","journal-title":"Immunity"},{"key":"2025032404080547500_r27","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1016\/j.jviromet.2007.05.021","article-title":"Detection of West Nile virus lineages 1 and 2 by real-time PCR","volume":"146","author":"Linke","year":"2007","journal-title":"J. Virol. Methods"},{"key":"2025032404080547500_r28","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1016\/j.immuni.2012.07.004","article-title":"The RIG-I-like receptor LGP2 controls CD8(+) T cell survival and fitness","volume":"37","author":"Suthar","year":"2012","journal-title":"Immunity"},{"key":"2025032404080547500_r29","doi-asserted-by":"crossref","first-page":"3361","DOI":"10.1128\/JVI.02368-12","article-title":"CD22 is required for protection against West Nile virus Infection","volume":"87","author":"Ma","year":"2013","journal-title":"J. Virol."},{"key":"2025032404080547500_r30","doi-asserted-by":"crossref","first-page":"e1003039","DOI":"10.1371\/journal.ppat.1003039","article-title":"IL-1\u03b2 signaling promotes CNS-intrinsic immune control of West Nile virus infection","volume":"8","author":"Ramos","year":"2012","journal-title":"PLoS Pathog."},{"key":"2025032404080547500_r31","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1111\/j.1600-065X.2010.00926.x","article-title":"Generation of effector CD8+ T cells and their conversion to memory T cells","volume":"236","author":"Cui","year":"2010","journal-title":"Immunol. Rev."},{"key":"2025032404080547500_r32","doi-asserted-by":"crossref","first-page":"3186","DOI":"10.4049\/jimmunol.1101649","article-title":"Regulatory T cells selectively control CD8+ T cell effector pool size via IL-2 restriction","volume":"187","author":"Kastenmuller","year":"2011","journal-title":"J. Immunol."},{"key":"2025032404080547500_r33","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1038\/ni.2029","article-title":"Regional and mucosal memory T cells","volume":"12","author":"Sheridan","year":"2011","journal-title":"Nat. Immunol."},{"key":"2025032404080547500_r34","doi-asserted-by":"crossref","first-page":"17872","DOI":"10.1073\/pnas.1010201107","article-title":"Memory T cells persisting within the brain after local infection show functional adaptations to their tissue of residence","volume":"107","author":"Wakim","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2025032404080547500_r35","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1046\/j.1365-2567.2001.01232.x","article-title":"Studies on transcriptional regulation of the mucosal T-cell integrin alphaEbeta7 (CD103)","volume":"103","author":"Robinson","year":"2001","journal-title":"Immunology"},{"key":"2025032404080547500_r36","doi-asserted-by":"crossref","first-page":"2413","DOI":"10.1126\/science.1058867","article-title":"Preferential localization of effector memory cells in nonlymphoid tissue","volume":"291","author":"Masopust","year":"2001","journal-title":"Science"},{"key":"2025032404080547500_r37","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1016\/S1074-7613(04)00103-7","article-title":"Dynamics of blood-borne CD8 memory T cell migration in vivo","volume":"20","author":"Klonowski","year":"2004","journal-title":"Immunity"},{"key":"2025032404080547500_r38","doi-asserted-by":"crossref","first-page":"4866","DOI":"10.4049\/jimmunol.1200402","article-title":"Antigen-independent differentiation and maintenance of effector-like resident memory T cells in tissues","volume":"188","author":"Casey","year":"2012","journal-title":"J. Immunol."}],"container-title":["The Journal of Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/192\/2\/683\/62509845\/1202153.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/192\/2\/683\/62509845\/1202153.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,24]],"date-time":"2025-03-24T00:49:31Z","timestamp":1742777371000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jimmunol\/article\/192\/2\/683\/7993417"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,1]]},"references-count":38,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2014,1,15]]}},"URL":"https:\/\/doi.org\/10.4049\/jimmunol.1202153","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.718206580.793490652","asserted-by":"object"}]},"ISSN":["0022-1767","1550-6606"],"issn-type":[{"value":"0022-1767","type":"print"},{"value":"1550-6606","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2014,1]]},"published":{"date-parts":[[2014,1]]}}}