{"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":1791221380230,"version":"4.1.0"},"reference-count":47,"publisher":"American Society for Microbiology","issue":"1","license":[{"start":{"date-parts":[[2015,1,1]],"date-time":"2015-01-01T00:00:00Z","timestamp":1420070400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Virol"],"published-print":{"date-parts":[[2015,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>It has been shown in various infection models that CD4<jats:sup>+<\/jats:sup>T cell help (T<jats:sub>H<\/jats:sub>) is necessary for the conditioning, maintenance, and\/or recall responses of memory CD8<jats:sup>+<\/jats:sup>T cells (CD8<jats:sub>M)<\/jats:sub>. Yet, in the case of vaccinia virus (VACV), which constitutes the vaccine used to eradicate smallpox and is a candidate vector for other infectious diseases, the issue is controversial because different groups have shown either T<jats:sub>H<\/jats:sub>dependence or independence of CD8<jats:sub>M<\/jats:sub>conditioning, maintenance, and\/or recall response. In agreement with some of these groups, we show that T<jats:sub>H<\/jats:sub>plays a role in, but is not essential for, the maintenance, proliferation, and effector differentiation of polyclonal memory CD8<jats:sup>+<\/jats:sup>T cells after infection with wild-type VACV strain Western Reserve. More important, we show that unhelped and helped anti-VACV memory CD8<jats:sup>+<\/jats:sup>T cells are similarly efficient at protecting susceptible mice from lethal mousepox, the mouse equivalent of human smallpox. Thus, T<jats:sub>H<\/jats:sub>is not essential for the conditioning and maintenance of memory CD8<jats:sup>+<\/jats:sup>T cells capable of mounting a recall response strong enough to protect from a lethal natural pathogen. Our results may partly explain why the VACV vaccine is so effective.<\/jats:p><jats:p><jats:bold>IMPORTANCE<\/jats:bold>We used vaccinia virus (VACV)\u2014a gold standard vaccine\u2014as the immunogen and ectromelia virus (ECTV) as the pathogen to demonstrate that the conditioning and maintenance of anti-VACV memory CD8<jats:sup>+<\/jats:sup>T cells and their ability to protect against an orthopoxvirus (OPV) infection in its natural host can develop in the absence of CD4<jats:sup>+<\/jats:sup>T cell help. Our results provide important insight to our basic knowledge of the immune system. Further, because VACV is used as a vaccine in humans, our results may help us understand how this vaccine induces protective immunity in this species. In addition, this work may partly explain why VACV is so effective as a vaccine.<\/jats:p>","DOI":"10.1128\/jvi.02176-14","type":"journal-article","created":{"date-parts":[[2014,10,30]],"date-time":"2014-10-30T07:04:02Z","timestamp":1414652642000},"page":"776-783","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":16,"title":["CD4<sup>+<\/sup>T Cell Help Is Dispensable for Protective CD8<sup>+<\/sup>T Cell Memory against Mousepox Virus following Vaccinia Virus Immunization"],"prefix":"10.1128","volume":"89","author":[{"given":"Min","family":"Fang","sequence":"first","affiliation":[{"name":"The Research Institute at Fox Chase Cancer Center, Immune Cell Development and Host Defense Program, Philadelphia, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanda","family":"Remakus","sequence":"additional","affiliation":[{"name":"The Research Institute at Fox Chase Cancer Center, Immune Cell Development and Host Defense Program, Philadelphia, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felicia","family":"Roscoe","sequence":"additional","affiliation":[{"name":"The Research Institute at Fox Chase Cancer Center, Immune Cell Development and Host Defense Program, Philadelphia, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xueying","family":"Ma","sequence":"additional","affiliation":[{"name":"The Research Institute at Fox Chase Cancer Center, Immune Cell Development and Host Defense Program, Philadelphia, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luis J.","family":"Sigal","sequence":"additional","affiliation":[{"name":"The Research Institute at Fox Chase Cancer Center, Immune Cell Development and Host Defense Program, Philadelphia, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.18.1.275"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/497194b"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.2174\/156652311795684731"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1586\/erv.11.79"},{"key":"e_1_3_2_6_2","volume-title":"Fields virology","author":"Fields BN","year":"2007","unstructured":"Fields BN, Knipe DM, Howley PM. 2007. Fields virology, 5th ed. Wolters Kluwer Health\/Lippincott Williams & Wilkins, Philadelphia, PA.","edition":"5"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.4161\/hv.21080"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.antiviral.2009.06.006"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2009.04.004"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.2010.00975.x"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2013.04.004"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0701822104"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201142205"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.175.7.4677"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.180.3.1517"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni1105"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1083317"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1200799"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0803545"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.177.11.8027"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0802041"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1003009"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.179.12.8243"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1001990"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0909945107"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI42056"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1002\/0471140864.ps0515s14"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.virol.2005.09.056"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20071854"},{"key":"e_1_3_2_30_2","first-page":"172","article-title":"Cross-presentation of self antigens to CD8+ T cells: the balance between tolerance and autoimmunity","volume":"215","author":"Kurts C","year":"1998","unstructured":"Kurts C, Heath WR, Carbone FR, Kosaka H, Miller JF. 1998. Cross-presentation of self antigens to CD8+ T cells: the balance between tolerance and autoimmunity. Novartis Found Symp 215:172\u2013181, discussion 181\u2013190.","journal-title":"Novartis Found Symp"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.175.10.6829"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20041912"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01281-10"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.171.1.27"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature03337"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2011.02.015"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00981-12"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201343805"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1082305"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.66.5.2617-2630.1992"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.8367726"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1993.tb05798.x"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1038\/353180a0"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20031961"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.173.4.2494"},{"key":"e_1_3_2_46_2","doi-asserted-by":"crossref","first-page":"2445","DOI":"10.4049\/jimmunol.131.5.2445","article-title":"Characterization of the murine T cell surface molecule, designated L3T4, identified by monoclonal antibody GK1.5: similarity of L3T4 to the human Leu-3\/T4 molecule","volume":"131","author":"Dialynas DP","year":"1983","unstructured":"Dialynas DP, Quan ZS, Wall KA, Pierres A, Quintans J, Loken MR, Pierres M, Fitch FW. 1983. Characterization of the murine T cell surface molecule, designated L3T4, identified by monoclonal antibody GK1.5: similarity of L3T4 to the human Leu-3\/T4 molecule. J Immunol 131:2445\u20132451.","journal-title":"J Immunol"},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.170.4.2053"},{"key":"e_1_3_2_48_2","doi-asserted-by":"crossref","first-page":"1698","DOI":"10.4049\/jimmunol.135.3.1698","article-title":"Inhibition of humoral immunity in vivo by monoclonal antibody to L3T4: studies with soluble antigens in intact mice","volume":"135","author":"Wofsy D","year":"1985","unstructured":"Wofsy D, Mayes DC, Woodcock J, Seaman WE. 1985. Inhibition of humoral immunity in vivo by monoclonal antibody to L3T4: studies with soluble antigens in intact mice. J Immunol 135:1698\u20131701.","journal-title":"J Immunol"}],"container-title":["Journal of Virology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/JVI.02176-14","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/JVI.02176-14","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,7,17]],"date-time":"2023-07-17T18:09:55Z","timestamp":1689617395000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/JVI.02176-14"}},"subtitle":[],"editor":[{"given":"G.","family":"McFadden","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2015,1]]},"references-count":47,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2015,1]]}},"alternative-id":["10.1128\/JVI.02176-14"],"URL":"https:\/\/doi.org\/10.1128\/jvi.02176-14","relation":{},"ISSN":["0022-538X","1098-5514"],"issn-type":[{"value":"0022-538X","type":"print"},{"value":"1098-5514","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,1]]},"assertion":[{"value":"2014-07-24","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2014-10-21","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2014-12-16","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}