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However, the lineage commitment of effector and memory Th cells in vivo following protein vaccination is poorly understood. In this study, we analyzed effector and memory CD4+ T cell differentiation in mice (Mus musculus) following adjuvanted glycoprotein immunization compared with acute lymphocytic choriomeningitis virus infection. Glycoprotein immunization induced CXCR5\u2212 non-Tfh effector and memory CD4+ T cells that surprisingly had not undergone polarization toward any particular Th cell lineage but had undergone memory differentiation. However, upon challenge with virus, these Th lineage\u2013nonpolarized memory CD4+ T cells were able to generate Th1 secondary effector cells, demonstrating their lineage plasticity. In addition, Tfh and memory Tfh cells were generated in response to protein immunization, and these cells differed from infection-induced Tfh cells by their lack of the transcription factor Tbet. Rechallenge experiments demonstrated that viral infection, but not protein immunization, during either the primary or secondary immune response, restricts the recall of Bcl6 expression and the generation of germinal center Tfh cells. Together, these data demonstrate that protein immunization generates a combination of nonpolarized memory cells that are highly plastic and memory Tfh cells that can undergo further Th1-like modulation during a secondary response to viral infection.<\/jats:p>","DOI":"10.4049\/jimmunol.2100210","type":"journal-article","created":{"date-parts":[[2021,8,11]],"date-time":"2021-08-11T18:00:14Z","timestamp":1628704814000},"page":"1388-1400","source":"Crossref","is-referenced-by-count":6,"title":["Protein Immunization Induces Memory CD4+ T Cells That Lack Th Lineage Commitment"],"prefix":"10.1093","volume":"207","author":[{"given":"Linda M","family":"Sircy","sequence":"first","affiliation":[{"name":"Department of Pathology, University of Utah , Salt Lake City, UT"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1280-5370","authenticated-orcid":false,"given":"Malia","family":"Harrison-Chau","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Utah , Salt Lake City, UT"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9111-3662","authenticated-orcid":false,"given":"Camille Leite","family":"Novis","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Utah , Salt Lake City, UT"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4572-9001","authenticated-orcid":false,"given":"Andrew","family":"Baessler","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Utah , Salt Lake City, UT"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jacklyn","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Utah , Salt Lake City, UT"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J Scott","family":"Hale","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Utah , Salt Lake City, UT"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2021,9,1]]},"reference":[{"key":"2025022610320996700_r1","doi-asserted-by":"crossref","first-page":"1557","DOI":"10.1182\/blood-2008-05-078154","article-title":"CD4 T cells: fates, functions, and faults","volume":"112","author":"Zhu","year":"2008","journal-title":"Blood"},{"key":"2025022610320996700_r2","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1016\/S0092-8674(00)80702-3","article-title":"A novel transcription factor, T-bet, directs Th1 lineage commitment","volume":"100","author":"Szabo","year":"2000","journal-title":"Cell"},{"key":"2025022610320996700_r3","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1016\/S0092-8674(00)80240-8","article-title":"The transcription factor GATA-3 is necessary and sufficient for Th2 cytokine gene expression in CD4 T cells","volume":"89","author":"Zheng","year":"1997","journal-title":"Cell"},{"key":"2025022610320996700_r4","doi-asserted-by":"crossref","first-page":"1121","DOI":"10.1016\/j.cell.2006.07.035","article-title":"The orphan nuclear receptor RORgammat directs the differentiation program of proinflammatory IL-17+ T helper cells","volume":"126","author":"Ivanov","year":"2006","journal-title":"Cell"},{"key":"2025022610320996700_r5","doi-asserted-by":"crossref","first-page":"1006","DOI":"10.1126\/science.1175870","article-title":"Bcl6 and Blimp-1 are reciprocal and antagonistic regulators of T follicular helper cell differentiation","volume":"325","author":"Johnston","year":"2009","journal-title":"Science"},{"key":"2025022610320996700_r6","doi-asserted-by":"crossref","first-page":"1001","DOI":"10.1126\/science.1176676","article-title":"Bcl6 mediates the development of T follicular helper cells","volume":"325","author":"Nurieva","year":"2009","journal-title":"Science"},{"key":"2025022610320996700_r7","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1016\/j.immuni.2009.07.002","article-title":"The transcriptional repressor Bcl-6 directs T follicular helper cell lineage commitment","volume":"31","author":"Yu","year":"2009","journal-title":"Immunity"},{"key":"2025022610320996700_r8","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1038\/ni.1837","article-title":"Effectors and memories: Bcl-6 and Blimp-1 in T and B lymphocyte differentiation","volume":"11","author":"Crotty","year":"2010","journal-title":"Nat. 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Med."},{"key":"2025022610320996700_r30","doi-asserted-by":"crossref","first-page":"1375","DOI":"10.1016\/j.vaccine.2007.12.038","article-title":"Vaccine adjuvant systems containing monophosphoryl lipid A and QS21 induce strong and persistent humoral and T cell responses against hepatitis B surface antigen in healthy adult volunteers","volume":"26","author":"Vandepapeli\u00e8re","year":"2008","journal-title":"Vaccine"},{"key":"2025022610320996700_r31","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1007\/978-1-4615-1823-5_10","article-title":"MF59. Design and evaluation of a safe and potent adjuvant for human vaccines","volume":"6","author":"Ott","year":"1995","journal-title":"Pharm. Biotechnol."},{"key":"2025022610320996700_r32","doi-asserted-by":"crossref","first-page":"1450","DOI":"10.1128\/IAI.68.3.1450-1456.2000","article-title":"CpG oligodeoxynucleotides act as adjuvants for pneumococcal polysaccharide-protein conjugate vaccines and enhance antipolysaccharide immunoglobulin G2a (IgG2a) and IgG3 antibodies","volume":"68","author":"Chu","year":"2000","journal-title":"Infect. Immun."},{"key":"2025022610320996700_r33","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1006\/cimm.1999.1572","article-title":"Immunostimulatory DNA pre-priming: a novel approach for prolonged Th1-biased immunity","volume":"198","author":"Kobayashi","year":"1999","journal-title":"Cell. 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Med."},{"key":"2025022610320996700_r43","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1002\/(SICI)1521-4141(199801)28:01<390::AID-IMMU390>3.0.CO;2-O","article-title":"Virus-specific MHC-class II-restricted TCR-transgenic mice: effects on humoral and cellular immune responses after viral infection","volume":"28","author":"Oxenius","year":"1998","journal-title":"Eur. J. Immunol."},{"key":"2025022610320996700_r44","doi-asserted-by":"crossref","first-page":"13990","DOI":"10.1128\/JVI.02273-14","article-title":"Activation of the RIG-I pathway during influenza vaccination enhances the germinal center reaction, promotes T follicular helper cell induction, and provides a dose-sparing effect and protective immunity","volume":"88","author":"Kulkarni","year":"2014","journal-title":"J. Virol."},{"key":"2025022610320996700_r45","doi-asserted-by":"crossref","first-page":"3558","DOI":"10.1016\/j.molimm.2008.05.010","article-title":"Molecular differences between the divergent responses of ovalbumin-specific CD4 T cells to alum-precipitated ovalbumin compared to ovalbumin expressed by Salmonella","volume":"45","author":"Serre","year":"2008","journal-title":"Mol. Immunol."},{"key":"2025022610320996700_r46","first-page":"641","article-title":"Tofacitinib inhibits the development of experimental autoimmune uveitis and reduces the proportions of Th1 but not of Th17 cells","volume":"26","author":"Bing","year":"2020","journal-title":"Mol. Vis."},{"key":"2025022610320996700_r47","doi-asserted-by":"crossref","first-page":"5874","DOI":"10.1038\/s41598-020-62543-5","article-title":"Synthetic mycobacterial molecular patterns partially complete Freund\u2019s adjuvant","volume":"10","author":"Dub\u00e9","year":"2020","journal-title":"Sci. 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Infect. Dis."},{"key":"2025022610320996700_r59","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1146\/annurev-immunol-031210-101400","article-title":"Follicular helper CD4 T cells (TFH)","volume":"29","author":"Crotty","year":"2011","journal-title":"Annu. Rev. Immunol."},{"key":"2025022610320996700_r60","doi-asserted-by":"crossref","first-page":"108232","DOI":"10.1016\/j.celrep.2020.108232","article-title":"Continued Bcl6 expression prevents the transdifferentiation of established Tfh cells into Th1 cells during acute viral infection","volume":"33","author":"Alterauge","year":"2020","journal-title":"Cell Rep."},{"key":"2025022610320996700_r61","doi-asserted-by":"crossref","first-page":"1001","DOI":"10.1084\/jem.20102144","article-title":"The lineage-defining factors T-bet and Bcl-6 collaborate to regulate Th1 gene expression patterns","volume":"208","author":"Oestreich","year":"2011","journal-title":"J. Exp. 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