{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,23]],"date-time":"2025-12-23T15:38:26Z","timestamp":1766504306455,"version":"3.40.3"},"reference-count":40,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2012,9,1]],"date-time":"2012-09-01T00:00:00Z","timestamp":1346457600000},"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":[[2012,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The precise immune components required for protection against a respiratory Orthopoxvirus infection, such as human smallpox or monkeypox, remain to be fully identified. In this study, we used the virulent Western Reserve strain of vaccinia virus (VACV-WR) to model a primary respiratory Orthopoxvirus infection. Naive mice infected with VACV-WR mounted an early CD8 T cell response directed against dominant and subdominant VACV-WR Ags, followed by a CD4 T cell and Ig response. In contrast to other VACV-WR infection models that highlight the critical requirement for CD4 T cells and Ig, we found that only mice deficient in CD8 T cells presented with severe cachexia, pulmonary inflammation, viral dissemination, and 100% mortality. Depletion of CD8 T cells at specified times throughout infection highlighted that they perform their critical function between days 4 and 6 postinfection and that their protective requirement is critically dictated by initial viral load and virulence. Finally, the ability of adoptively transferred naive CD8 T cells to protect RAG\u2212\/\u2212 mice against a lethal VACV-WR infection demonstrated that they are both necessary and sufficient in protecting against a primary VACV-WR infection of the respiratory tract.<\/jats:p>","DOI":"10.4049\/jimmunol.1200799","type":"journal-article","created":{"date-parts":[[2012,7,24]],"date-time":"2012-07-24T04:17:09Z","timestamp":1343103429000},"page":"2432-2440","source":"Crossref","is-referenced-by-count":49,"title":["CD8 T Cells Are Essential for Recovery from a Respiratory Vaccinia Virus Infection"],"prefix":"10.1093","volume":"189","author":[{"given":"John","family":"Goulding","sequence":"first","affiliation":[{"name":"Division of Immune Regulation, La Jolla Institute for Allergy and Immunology , San Diego, CA 92037"},{"name":"Department of Pathology, Immunology, and Laboratory Medicine, University of Florida , Gainesville, FL 32610-0275"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rebecka","family":"Bogue","sequence":"additional","affiliation":[{"name":"Division of Immune Regulation, La Jolla Institute for Allergy and Immunology , San Diego, CA 92037"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vikas","family":"Tahiliani","sequence":"additional","affiliation":[{"name":"Division of Immune Regulation, La Jolla Institute for Allergy and Immunology , San Diego, CA 92037"},{"name":"Department of Pathology, Immunology, and Laboratory Medicine, University of Florida , Gainesville, FL 32610-0275"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Croft","sequence":"additional","affiliation":[{"name":"Division of Immune Regulation, La Jolla Institute for Allergy and Immunology , San Diego, CA 92037"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shahram","family":"Salek-Ardakani","sequence":"additional","affiliation":[{"name":"Division of Immune Regulation, La Jolla Institute for Allergy and Immunology , San Diego, CA 92037"},{"name":"Department of Pathology, Immunology, and Laboratory Medicine, University of Florida , Gainesville, FL 32610-0275"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2012,9,1]]},"reference":[{"key":"2025032409223667500_r1","doi-asserted-by":"crossref","first-page":"472","DOI":"10.1016\/j.tim.2008.07.009","article-title":"Vaccinia virus morphogenesis and dissemination","volume":"16","author":"Roberts","year":"2008","journal-title":"Trends Microbiol."},{"key":"2025032409223667500_r2","doi-asserted-by":"crossref","first-page":"681","DOI":"10.3201\/eid1704.101865","article-title":"Should remaining stockpiles of smallpox virus (variola) be destroyed?","volume":"17","author":"Weinstein","year":"2011","journal-title":"Emerg. Infect. Dis."},{"key":"2025032409223667500_r3","doi-asserted-by":"crossref","first-page":"2127","DOI":"10.1001\/jama.281.22.2127","article-title":"Smallpox as a biological weapon: medical and public health management","volume":"281","author":"Henderson","year":"1999","journal-title":"JAMA"},{"key":"2025032409223667500_r4","doi-asserted-by":"crossref","first-page":"16262","DOI":"10.1073\/pnas.1005769107","article-title":"Major increase in human monkeypox incidence 30 years after smallpox vaccination campaigns cease in the Democratic Republic of Congo","volume":"107","author":"Rimoin","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2025032409223667500_r5","doi-asserted-by":"crossref","first-page":"189","DOI":"10.3201\/eid1801.110692","article-title":"Vaccinia virus zoonotic infection, S\u00e3o Paulo State, Brazil","volume":"18","author":"Megid","year":"2012","journal-title":"Emerg. Infect. Dis."},{"key":"2025032409223667500_r6","doi-asserted-by":"crossref","first-page":"1263","DOI":"10.1056\/NEJM198011273032204","article-title":"The confirmation and maintenance of smallpox eradication","volume":"303","author":"Breman","year":"1980","journal-title":"N. Engl. J. Med."},{"key":"2025032409223667500_r7","doi-asserted-by":"crossref","first-page":"6265","DOI":"10.4049\/jimmunol.172.10.6265","article-title":"Cellular and humoral immunity against vaccinia virus infection of mice","volume":"172","author":"Xu","year":"2004","journal-title":"J. Immunol."},{"key":"2025032409223667500_r8","doi-asserted-by":"crossref","first-page":"6070","DOI":"10.1073\/pnas.89.13.6070","article-title":"Beta 2-microglobulin-, CD8+ T-cell-deficient mice survive inoculation with high doses of vaccinia virus and exhibit altered IgG responses","volume":"89","author":"Spriggs","year":"1992","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2025032409223667500_r9","doi-asserted-by":"crossref","first-page":"6333","DOI":"10.1128\/JVI.00115-06","article-title":"Protective immunity against secondary poxvirus infection is dependent on antibody but not on CD4 or CD8 T-cell function","volume":"80","author":"Panchanathan","year":"2006","journal-title":"J. Virol."},{"key":"2025032409223667500_r10","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1038\/sj.icb.7100118","article-title":"Correlates of protective immunity in poxvirus infection: where does antibody stand?","volume":"86","author":"Panchanathan","year":"2008","journal-title":"Immunol. Cell Biol."},{"key":"2025032409223667500_r11","doi-asserted-by":"crossref","first-page":"9458","DOI":"10.1073\/pnas.1233578100","article-title":"Shared modes of protection against poxvirus infection by attenuated and conventional smallpox vaccine viruses","volume":"100","author":"Belyakov","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2025032409223667500_r12","doi-asserted-by":"crossref","first-page":"2761","DOI":"10.1099\/0022-1317-71-11-2761","article-title":"Biological characterization of recombinant vaccinia viruses in mice infected by the respiratory route","volume":"71","author":"Williamson","year":"1990","journal-title":"J. Gen. Virol."},{"key":"2025032409223667500_r13","first-page":"289","article-title":"Mouse models for studying orthopoxvirus respiratory infections","volume":"269","author":"Schriewer","year":"2004","journal-title":"Methods Mol. Biol."},{"key":"2025032409223667500_r14","doi-asserted-by":"crossref","first-page":"852","DOI":"10.1177\/0300985810378649","article-title":"Animal models of orthopoxvirus infection","volume":"47","author":"Chapman","year":"2010","journal-title":"Vet. Pathol."},{"key":"2025032409223667500_r15","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1128\/br.23.2.61-95.1959","article-title":"Response of mice to ectromelia and vaccinia viruses","volume":"23","author":"Briody","year":"1959","journal-title":"Bacteriol. Rev."},{"key":"2025032409223667500_r16","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1099\/0022-1317-1-3-399","article-title":"Respiratory infection of mice with vaccinia virus","volume":"1","author":"Turner","year":"1967","journal-title":"J. Gen. Virol."},{"key":"2025032409223667500_r17","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1186\/1743-422X-4-22","article-title":"Pathogeneses of respiratory infections with virulent and attenuated vaccinia viruses","volume":"4","author":"Hayasaka","year":"2007","journal-title":"Virol. J."},{"key":"2025032409223667500_r18","doi-asserted-by":"crossref","first-page":"1973","DOI":"10.1099\/vir.0.19285-0","article-title":"A kinetic analysis of immune mediators in the lungs of mice infected with vaccinia virus and comparison with intradermal infection","volume":"84","author":"Reading","year":"2003","journal-title":"J. Gen. Virol."},{"key":"2025032409223667500_r19","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1084\/jem.68.3.401","article-title":"The Behavior of Pox Viruses in the Respiratory Tract: I. The Response of Mice to the Nasal Instillation of Vaccinia Virus","volume":"68","author":"Nelson","year":"1938","journal-title":"J. Exp. Med."},{"key":"2025032409223667500_r20","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1016\/j.virol.2005.06.049","article-title":"Bioluminescence imaging of vaccinia virus: effects of interferon on viral replication and spread","volume":"341","author":"Luker","year":"2005","journal-title":"Virology"},{"key":"2025032409223667500_r21","doi-asserted-by":"crossref","first-page":"e1000811","DOI":"10.1371\/journal.ppat.1000811","article-title":"Direct TLR2 signaling is critical for NK cell activation and function in response to vaccinia viral infection","volume":"6","author":"Martinez","year":"2010","journal-title":"PLoS Pathog."},{"key":"2025032409223667500_r22","doi-asserted-by":"crossref","first-page":"1219","DOI":"10.1084\/jem.20082835","article-title":"Inhibition of NK cell activity by IL-17 allows vaccinia virus to induce severe skin lesions in a mouse model of eczema vaccinatum","volume":"206","author":"Kawakami","year":"2009","journal-title":"J. Exp. Med."},{"key":"2025032409223667500_r23","doi-asserted-by":"crossref","first-page":"2540","DOI":"10.1128\/JVI.01884-08","article-title":"Modified vaccinia virus ankara triggers chemotaxis of monocytes and early respiratory immigration of leukocytes by induction of CCL2 expression","volume":"83","author":"Lehmann","year":"2009","journal-title":"J. Virol."},{"key":"2025032409223667500_r24","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1186\/1743-422X-1-10","article-title":"Susceptibility of different leukocyte cell types to Vaccinia virus infection","volume":"1","author":"S\u00e1nchez-Puig","year":"2004","journal-title":"Virol. J."},{"key":"2025032409223667500_r25","doi-asserted-by":"crossref","first-page":"952","DOI":"10.4049\/jimmunol.1004164","article-title":"Cutting edge: Protective effect of CX3CR1+ dendritic cells in a vaccinia virus pulmonary infection model","volume":"188","author":"Bonduelle","year":"2012","journal-title":"J. Immunol."},{"key":"2025032409223667500_r26","doi-asserted-by":"crossref","first-page":"7969","DOI":"10.4049\/jimmunol.181.11.7969","article-title":"OX40 drives protective vaccinia virus-specific CD8 T cells","volume":"181","author":"Salek-Ardakani","year":"2008","journal-title":"J. Immunol."},{"key":"2025032409223667500_r27","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1172\/JCI42056","article-title":"The TNFR family members OX40 and CD27 link viral virulence to protective T cell vaccines in mice","volume":"121","author":"Salek-Ardakani","year":"2011","journal-title":"J. Clin. Invest."},{"key":"2025032409223667500_r28","doi-asserted-by":"crossref","first-page":"6278","DOI":"10.4049\/jimmunol.0803682","article-title":"The adaptor molecule MyD88 directly promotes CD8 T cell responses to vaccinia virus","volume":"182","author":"Zhao","year":"2009","journal-title":"J. Immunol."},{"key":"2025032409223667500_r29","doi-asserted-by":"crossref","first-page":"6814","DOI":"10.4049\/jimmunol.178.11.6814","article-title":"Vaccinia virus-specific CD4+ T cell responses target a set of antigens largely distinct from those targeted by CD8+ T cell responses","volume":"178","author":"Moutaftsi","year":"2007","journal-title":"J. Immunol."},{"key":"2025032409223667500_r30","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1084\/jem.20041912","article-title":"Identification of poxvirus CD8+ T cell determinants to enable rational design and characterization of smallpox vaccines","volume":"201","author":"Tscharke","year":"2005","journal-title":"J. Exp. Med."},{"key":"2025032409223667500_r31","doi-asserted-by":"crossref","first-page":"817","DOI":"10.1038\/nbt1215","article-title":"A consensus epitope prediction approach identifies the breadth of murine T(CD8+)-cell responses to vaccinia virus","volume":"24","author":"Moutaftsi","year":"2006","journal-title":"Nat. Biotechnol."},{"key":"2025032409223667500_r32","doi-asserted-by":"crossref","first-page":"11724","DOI":"10.1128\/JVI.79.18.11724-11733.2005","article-title":"Vaccinia virus H3L envelope protein is a major target of neutralizing antibodies in humans and elicits protection against lethal challenge in mice","volume":"79","author":"Davies","year":"2005","journal-title":"J. Virol."},{"key":"2025032409223667500_r33","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1016\/j.vaccine.2009.09.086","article-title":"The smallpox vaccine induces an early neutralizing IgM response","volume":"28","author":"Moyron-Quiroz","year":"2009","journal-title":"Vaccine"},{"key":"2025032409223667500_r34","doi-asserted-by":"crossref","first-page":"5294","DOI":"10.4049\/jimmunol.1100406","article-title":"B cell-specific expression of B7-2 is required for follicular Th cell function in response to vaccinia virus","volume":"186","author":"Salek-Ardakani","year":"2011","journal-title":"J. Immunol."},{"key":"2025032409223667500_r35","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1038\/nri2941","article-title":"Recombination centres and the orchestration of V(D)J recombination","volume":"11","author":"Schatz","year":"2011","journal-title":"Nat. Rev. Immunol."},{"key":"2025032409223667500_r36","doi-asserted-by":"crossref","first-page":"2909","DOI":"10.4049\/jimmunol.0803545","article-title":"Preferential use of B7.2 and not B7.1 in priming of vaccinia virus-specific CD8 T cells","volume":"182","author":"Salek-Ardakani","year":"2009","journal-title":"J. Immunol."},{"key":"2025032409223667500_r37","doi-asserted-by":"crossref","first-page":"5016","DOI":"10.1128\/JVI.02359-10","article-title":"Deletion of major nonessential genomic regions in the vaccinia virus Lister strain enhances attenuation without altering vaccine efficacy in mice","volume":"85","author":"Dimier","year":"2011","journal-title":"J. Virol."},{"key":"2025032409223667500_r38","doi-asserted-by":"crossref","first-page":"7713","DOI":"10.1128\/JVI.76.15.7713-7723.2002","article-title":"Immunogenicity and safety of defective vaccinia virus lister: comparison with modified vaccinia virus Ankara","volume":"76","author":"Ober","year":"2002","journal-title":"J. Virol."},{"key":"2025032409223667500_r39","doi-asserted-by":"crossref","first-page":"8301","DOI":"10.1128\/jvi.70.12.8301-8309.1996","article-title":"Different roles for CD4+ and CD8+ T lymphocytes and macrophage subsets in the control of a generalized virus infection","volume":"70","author":"Karupiah","year":"1996","journal-title":"J. Virol."},{"key":"2025032409223667500_r40","doi-asserted-by":"crossref","first-page":"6829","DOI":"10.4049\/jimmunol.175.10.6829","article-title":"Antibodies and CD8+ T cells are complementary and essential for natural resistance to a highly lethal cytopathic virus","volume":"175","author":"Fang","year":"2005","journal-title":"J. Immunol."}],"container-title":["The Journal of Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/189\/5\/2432\/61714106\/1200799.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/189\/5\/2432\/61714106\/1200799.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,27]],"date-time":"2025-03-27T05:40:46Z","timestamp":1743054046000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jimmunol\/article\/189\/5\/2432\/7993597"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,9,1]]},"references-count":40,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2012,9,1]]}},"URL":"https:\/\/doi.org\/10.4049\/jimmunol.1200799","relation":{},"ISSN":["0022-1767","1550-6606"],"issn-type":[{"type":"print","value":"0022-1767"},{"type":"electronic","value":"1550-6606"}],"subject":[],"published-other":{"date-parts":[[2012,9]]},"published":{"date-parts":[[2012,9,1]]}}}