{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T23:09:09Z","timestamp":1788390549519,"version":"build-2803163510"},"reference-count":81,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2023,10,26]],"date-time":"2023-10-26T00:00:00Z","timestamp":1698278400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["DFG Di 714\/20-1"],"award-info":[{"award-number":["DFG Di 714\/20-1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>Antiretroviral therapy (ART) transformed HIV from a life-threatening disease to a chronic condition. However, eliminating the virus remains an elusive therapy goal. For several decades, Friend virus (FV) infection serves as a murine model to study retrovirus immunity. Similar to HIV, FV persists at low levels in lymph nodes B cell follicles avoiding elimination by immune cells. Such immune-privileged reservoirs exclude cytotoxic T cells from entry. However, CXCR5<jats:sup>+<\/jats:sup>T cells are permitted to traffic through germinal centers. This marker is predominantly expressed by CD4<jats:sup>+<\/jats:sup>follicular helper T cells (Tfh). Therefore, we explored immunotherapy to induce cytotoxic Tfh, which are rarely found under physiological conditions. The TNF receptor family member CD137 was first identified as a promising target for cancer immunotherapy. We demonstrated that FV-infected mice treatment with \u03b1CD137 antibody resulted in an induction of the cytotoxic program in Tfh. The therapy significantly increased numbers of cytotoxic Tfh within B cell follicles and contributed to viral load reduction. Moreover, \u03b1CD137 antibody combined with ART delayed virus rebound upon treatment termination without disturbing the lymph node architecture or antibody responses. Thus, \u03b1CD137 antibody therapy might be a novel strategy to target the retroviral reservoir and an interesting approach for HIV cure research.<\/jats:p>","DOI":"10.1371\/journal.ppat.1011725","type":"journal-article","created":{"date-parts":[[2023,10,26]],"date-time":"2023-10-26T17:52:31Z","timestamp":1698342751000},"page":"e1011725","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":5,"title":["Immunotherapy-induced cytotoxic T follicular helper cells reduce numbers of retrovirus-infected reservoir cells in B cell follicles"],"prefix":"10.1371","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5199-5472","authenticated-orcid":true,"given":"Anna","family":"Malyshkina","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wibke","family":"Bayer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip","family":"Podschwadt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucas","family":"Otto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zehra","family":"Karakoese","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathrin","family":"Sutter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kirsten","family":"Bruderek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baoxiao","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kerry J.","family":"Lavender","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario L.","family":"Santiago","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pia Madeleine","family":"Leipe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carina","family":"Elsner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Esser","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sven","family":"Brandau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"Gunzer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulf","family":"Dittmer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2023,10,26]]},"reference":[{"issue":"7","key":"ppat.1011725.ref001","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1038\/nm.4138","article-title":"Follicular T helper cells: hotspots for HIV-1 persistence","volume":"22","author":"M Paiardini","year":"2016","journal-title":"Nat Med"},{"issue":"1","key":"ppat.1011725.ref002","first-page":"33","article-title":"Follicular CD8+ T Cells Are Elevated in HIV Infection and Induce PD-L1 on","volume":"210","author":"LE Martinez","year":"2023","journal-title":"B Cells. J Immunol"},{"key":"ppat.1011725.ref003","doi-asserted-by":"crossref","first-page":"708874","DOI":"10.3389\/fimmu.2021.708874","article-title":"CD8(+) Regulatory T Cell\u2014A Mystery to Be Revealed","volume":"12","author":"S Mishra","year":"2021","journal-title":"Front Immunol"},{"issue":"5","key":"ppat.1011725.ref004","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1093\/femsre\/fuz012","article-title":"Friend retrovirus studies reveal complex interactions between intrinsic, innate and adaptive immunity","volume":"43","author":"U Dittmer","year":"2019","journal-title":"FEMS Microbiol Rev"},{"issue":"2","key":"ppat.1011725.ref005","doi-asserted-by":"crossref","first-page":"e1006776","DOI":"10.1371\/journal.ppat.1006776","article-title":"Regulatory T cells in retroviral infections.","volume":"14","author":"KJ Hasenkrug","year":"2018","journal-title":"PLoS Pathog.PubMed Central PMCID"},{"issue":"1","key":"ppat.1011725.ref006","doi-asserted-by":"crossref","DOI":"10.1128\/mBio.00004-19","article-title":"Infection of B Cell Follicle-Resident Cells by Friend Retrovirus Occurs during Acute Infection and Is Maintained during Viral Persistence","volume":"10","author":"S Windmann","year":"2019","journal-title":"mBio"},{"issue":"11","key":"ppat.1011725.ref007","doi-asserted-by":"crossref","first-page":"5613","DOI":"10.4049\/jimmunol.1401161","article-title":"Compartmentalization of simian immunodeficiency virus replication within secondary lymphoid tissues of rhesus macaques is linked to disease stage and inversely related to localization of virus-specific CTL","volume":"193","author":"E Connick","year":"2014","journal-title":"J Immunol"},{"issue":"2","key":"ppat.1011725.ref008","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1038\/nm.3781","article-title":"B cell follicle sanctuary permits persistent productive simian immunodeficiency virus infection in elite controllers","volume":"21","author":"Y Fukazawa","year":"2015","journal-title":"Nat Med"},{"issue":"5","key":"ppat.1011725.ref009","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1089\/aid.2005.21.363","article-title":"Lymphoid follicles are sites of heightened human immunodeficiency virus type 1 (HIV-1) replication and reduced antiretroviral effector mechanisms.","volume":"21","author":"JM Folkvord","year":"2005","journal-title":"AIDS Res Hum Retroviruses"},{"key":"ppat.1011725.ref010","doi-asserted-by":"crossref","first-page":"2362","DOI":"10.3389\/fimmu.2019.02362","article-title":"Does B Cell Follicle Exclusion of CD8+ T Cells Make Lymph Nodes Sanctuaries of HIV Replication?","volume":"10","author":"SE Beck","year":"2019","journal-title":"Front Immunol."},{"issue":"1","key":"ppat.1011725.ref011","first-page":"7785","article-title":"Fas Ligand-mediated cytotoxicity of CD4+ T cells during chronic retrovirus infection.","volume":"7","author":"A Malyshkina","year":"2017","journal-title":"Sci Rep.PubMed Central PMCID"},{"key":"ppat.1011725.ref012","first-page":"4","article-title":"Follicular regulatory T cells inhibit the development of granzyme B-expressing follicular helper T cells","author":"MM Xie","year":"2019","journal-title":"JCI Insight"},{"issue":"10","key":"ppat.1011725.ref013","doi-asserted-by":"crossref","first-page":"1243","DOI":"10.1007\/s00262-016-1829-2","article-title":"4-1BB agonism: adding the accelerator to cancer immunotherapy","volume":"65","author":"C Chester","year":"2016","journal-title":"Cancer Immunol Immunother"},{"issue":"5647","key":"ppat.1011725.ref014","doi-asserted-by":"crossref","first-page":"1041","DOI":"10.1126\/science.1090148","article-title":"Control of effector CD8+ T cell function by the transcription factor Eomesodermin","volume":"302","author":"EL Pearce","year":"2003","journal-title":"Science"},{"issue":"1","key":"ppat.1011725.ref015","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1182\/blood-2017-06-741041","article-title":"Immunotherapy targeting 4-1BB: mechanistic rationale, clinical results, and future strategies","volume":"131","author":"C Chester","year":"2018","journal-title":"Blood"},{"issue":"1","key":"ppat.1011725.ref016","doi-asserted-by":"crossref","first-page":"2141","DOI":"10.1038\/s41467-019-10088-1","article-title":"Optimization of 4-1BB antibody for cancer immunotherapy by balancing agonistic strength with FcgammaR affinity","volume":"10","author":"X Qi","year":"2019","journal-title":"Nat Commun"},{"issue":"12","key":"ppat.1011725.ref017","doi-asserted-by":"crossref","first-page":"2784","DOI":"10.1002\/ijc.23457","article-title":"Eradication of established renal cell carcinoma by a combination of 5-fluorouracil and anti-4-1BB monoclonal antibody in mice","volume":"122","author":"SA Ju","year":"2008","journal-title":"Int J Cancer"},{"issue":"7","key":"ppat.1011725.ref018","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1016\/j.biopha.2008.10.003","article-title":"CD137 enhances cytotoxicity of CD3(+)CD56(+) cells and their capacities to induce CD4(+) Th1 responses.","volume":"63","author":"BQ Zhu","year":"2009","journal-title":"Biomed Pharmacother"},{"issue":"3","key":"ppat.1011725.ref019","doi-asserted-by":"crossref","first-page":"1116","DOI":"10.1002\/(SICI)1521-4141(199803)28:03<1116::AID-IMMU1116>3.0.CO;2-A","article-title":"Amplification of tumor immunity by gene transfer of the co-stimulatory 4-1BB ligand: synergy with the CD28 co-stimulatory pathway","volume":"28","author":"I Melero","year":"1998","journal-title":"Eur J Immunol"},{"issue":"8","key":"ppat.1011725.ref020","doi-asserted-by":"crossref","first-page":"5003","DOI":"10.4049\/jimmunol.162.8.5003","article-title":"4-1BBL cooperates with B7-1 and B7-2 in converting a B cell lymphoma cell line into a long-lasting antitumor vaccine","volume":"162","author":"BA Guinn","year":"1999","journal-title":"J Immunol"},{"issue":"5","key":"ppat.1011725.ref021","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1172\/JCI0214184","article-title":"Provision of antigen and CD137 signaling breaks immunological ignorance, promoting regression of poorly immunogenic tumors","volume":"109","author":"RA Wilcox","year":"2002","journal-title":"J Clin Invest"},{"issue":"3","key":"ppat.1011725.ref022","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1007\/s00262-019-02300-4","article-title":"Chronic retroviral infection of mice promotes tumor development, but CD137 agonist therapy restores effective tumor immune surveillance","volume":"68","author":"A Malyshkina","year":"2019","journal-title":"Cancer Immunol Immunother"},{"key":"ppat.1011725.ref023","doi-asserted-by":"crossref","first-page":"10281","DOI":"10.1038\/ncomms10281","article-title":"Stepwise B-cell-dependent expansion of T helper clonotypes diversifies the T-cell response.","volume":"7","author":"J Merkenschlager","year":"2016","journal-title":"Nat Commun.PubMed Central PMCID"},{"key":"ppat.1011725.ref024","first-page":"91","article-title":"Mechanisms of control of acute Friend virus infection by CD4+ T helper cells and their functional impairment by regulatory T cells","author":"SR Nair","year":"2010","journal-title":"J Gen Virol"},{"key":"ppat.1011725.ref025","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1007\/978-1-4939-2498-1_1","article-title":"Identification of mouse T follicular helper cells by flow cytometry","volume":"1291","author":"AP Meli","year":"2015","journal-title":"Methods Mol Biol"},{"issue":"11","key":"ppat.1011725.ref026","doi-asserted-by":"crossref","first-page":"6306","DOI":"10.1128\/JVI.00432-13","article-title":"CD4+ T cells develop antiretroviral cytotoxic activity in the absence of regulatory T cells and CD8+ T cells","volume":"87","author":"N Manzke","year":"2013","journal-title":"J Virol"},{"key":"ppat.1011725.ref027","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1007\/978-1-4939-8885-3_7","article-title":"CD107a Degranulation Assay to Evaluate Immune Cell Antitumor Activity","volume":"1884","author":"S Lorenzo-Herrero","year":"2019","journal-title":"Methods Mol Biol"},{"issue":"8","key":"ppat.1011725.ref028","doi-asserted-by":"crossref","first-page":"2423","DOI":"10.1182\/blood-2010-08-301945","article-title":"CD137 stimulation enhances the antilymphoma activity of anti-CD20 antibodies","volume":"117","author":"HE Kohrt","year":"2011","journal-title":"Blood"},{"issue":"1","key":"ppat.1011725.ref029","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/j.immuni.2015.12.011","article-title":"Circulating HIV-Specific Interleukin-21(+)CD4(+) T Cells Represent Peripheral Tfh Cells with Antigen-Dependent Helper Functions.","volume":"44","author":"BT Schultz","year":"2016","journal-title":"Immunity"},{"issue":"21","key":"ppat.1011725.ref030","doi-asserted-by":"crossref","first-page":"6895","DOI":"10.1158\/1078-0432.CCR-08-0285","article-title":"Therapeutic antitumor efficacy of anti-CD137 agonistic monoclonal antibody in mouse models of myeloma","volume":"14","author":"O Murillo","year":"2008","journal-title":"Clin Cancer Res"},{"issue":"6","key":"ppat.1011725.ref031","doi-asserted-by":"crossref","first-page":"682","DOI":"10.1038\/nm0697-682","article-title":"Monoclonal antibodies against the 4-1BB T-cell activation molecule eradicate established tumors","volume":"3","author":"I Melero","year":"1997","journal-title":"Nat Med"},{"issue":"6","key":"ppat.1011725.ref032","doi-asserted-by":"crossref","first-page":"536","DOI":"10.1038\/ni798","article-title":"In vivo stimulation of CD137 broadens primary antiviral CD8+ T cell responses","volume":"3","author":"ES Halstead","year":"2002","journal-title":"Nat Immunol"},{"issue":"4","key":"ppat.1011725.ref033","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1016\/j.chom.2020.03.014","article-title":"The Biology of the HIV-1 Latent Reservoir and Implications for Cure Strategies.","volume":"27","author":"LB Cohn","year":"2020","journal-title":"Cell Host Microbe."},{"issue":"12","key":"ppat.1011725.ref034","first-page":"2249","article-title":"Friend leukemia virus spleen focus assay: relationship of spleen foci to viremia, splenomegaly, and survival time","volume":"27","author":"MA Chirigos","year":"1967","journal-title":"Cancer Res"},{"issue":"6260","key":"ppat.1011725.ref035","doi-asserted-by":"crossref","first-page":"762","DOI":"10.1038\/343762a0","article-title":"Activation of cell growth by binding of Friend spleen focus-forming virus gp55 glycoprotein to the erythropoietin receptor","volume":"343","author":"JP Li","year":"1990","journal-title":"Nature"},{"key":"ppat.1011725.ref036","article-title":"Comparative Evaluation of the Vaccine Efficacies of Three Adenovirus-Based Vector Types in the Friend Retrovirus Infection Model","author":"CP Hrycak","year":"2019","journal-title":"J Virol"},{"key":"ppat.1011725.ref037","first-page":"1","article-title":"Host-directed immunotherapy of viral and bacterial infections: past, present and future","volume":"2022","author":"RS Wallis","year":"2022","journal-title":"Nat Rev Immunol"},{"issue":"629","key":"ppat.1011725.ref038","doi-asserted-by":"crossref","DOI":"10.1126\/scitranslmed.abl3836","article-title":"Pembrolizumab induces HIV latency reversal in people living with HIV and cancer on antiretroviral therapy","volume":"14","author":"TS Uldrick","year":"2022","journal-title":"Sci Transl Med"},{"issue":"1","key":"ppat.1011725.ref039","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1038\/s41591-021-01643-9","article-title":"A guide to immunotherapy for COVID-19","volume":"28","author":"FL van de Veerdonk","year":"2022","journal-title":"Nat Med"},{"issue":"8","key":"ppat.1011725.ref040","doi-asserted-by":"crossref","first-page":"1929","DOI":"10.1158\/1078-0432.CCR-16-1272","article-title":"Results from an Integrated Safety Analysis of Urelumab, an Agonist Anti-CD137 Monoclonal Antibody","volume":"23","author":"NH Segal","year":"2017","journal-title":"Clin Cancer Res"},{"issue":"8","key":"ppat.1011725.ref041","doi-asserted-by":"crossref","first-page":"1816","DOI":"10.1158\/1078-0432.CCR-17-1922","article-title":"Phase I Study of Single-Agent Utomilumab (PF-05082566), a 4-1BB\/CD137 Agonist, in Patients with Advanced Cancer.","volume":"24","author":"NH Segal","year":"2018","journal-title":"Clin Cancer Res"},{"issue":"1","key":"ppat.1011725.ref042","doi-asserted-by":"crossref","first-page":"4679","DOI":"10.1038\/s41467-018-07136-7","article-title":"Structure of the 4-1BB\/4-1BBL complex and distinct binding and functional properties of utomilumab and urelumab.","volume":"9","author":"SM Chin","year":"2018","journal-title":"Nat Commun."},{"issue":"10","key":"ppat.1011725.ref043","doi-asserted-by":"crossref","DOI":"10.3390\/cancers13102288","article-title":"CD137 as an Attractive T Cell Co-Stimulatory Target in the TNFRSF for Immuno-Oncology Drug Development.","volume":"13","author":"K. Hashimoto","year":"2021","journal-title":"Cancers (Basel)."},{"issue":"1","key":"ppat.1011725.ref044","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1186\/s12967-022-03619-w","article-title":"A humanized 4-1BB-targeting agonistic antibody exerts potent antitumor activity in colorectal cancer without systemic toxicity","volume":"20","author":"LS Cheng","year":"2022","journal-title":"J Transl Med"},{"key":"ppat.1011725.ref045","doi-asserted-by":"crossref","first-page":"954602","DOI":"10.1155\/2011\/954602","article-title":"Cytotoxic CD4 T cells in antiviral immunity","volume":"2011","author":"NB Marshall","year":"2011","journal-title":"J Biomed Biotechnol"},{"issue":"2","key":"ppat.1011725.ref046","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1038\/nri3152","article-title":"Expanding roles for CD4(+) T cells in immunity to viruses.","volume":"12","author":"SL Swain","year":"2012","journal-title":"Nat Rev Immunol"},{"issue":"12","key":"ppat.1011725.ref047","doi-asserted-by":"crossref","DOI":"10.3390\/v11121136","article-title":"Insight into the Tropism of Dengue Virus in Humans.","volume":"11","author":"F Begum","year":"2019","journal-title":"Viruses."},{"key":"ppat.1011725.ref048","first-page":"10","article-title":"HTLV-1, the Other Pathogenic Yet Neglected Human Retrovirus: From Transmission to Therapeutic Treatment.","author":"N Futsch","year":"2017","journal-title":"Viruses."},{"issue":"6884","key":"ppat.1011725.ref049","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1038\/417095a","article-title":"HIV preferentially infects HIV-specific CD4+ T cells","volume":"417","author":"DC Douek","year":"2002","journal-title":"Nature"},{"issue":"37","key":"ppat.1011725.ref050","doi-asserted-by":"crossref","first-page":"13439","DOI":"10.1073\/pnas.1400446111","article-title":"Preferential infection of human Ad5-specific CD4 T cells by HIV in Ad5 naturally exposed and recombinant Ad5-HIV vaccinated individuals","volume":"111","author":"H Hu","year":"2014","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ppat.1011725.ref051","doi-asserted-by":"crossref","first-page":"895","DOI":"10.3389\/fimmu.2018.00895","article-title":"Follicular CD4 T Helper Cells As a Major HIV Reservoir Compartment: A Molecular Perspective.","volume":"9","author":"M Aid","year":"2018","journal-title":"Front Immunol."},{"issue":"1","key":"ppat.1011725.ref052","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1093\/infdis\/jiz431","article-title":"Follicular Helper T Cells Are Major Human Immunodeficiency Virus-2 Reservoirs and Support Productive Infection","volume":"221","author":"A Godinho-Santos","year":"2020","journal-title":"J Infect Dis"},{"key":"ppat.1011725.ref053","doi-asserted-by":"crossref","first-page":"1844","DOI":"10.3389\/fimmu.2019.01844","article-title":"Maintenance of Functional CD57+ Cytolytic CD4+ T Cells in HIV+ Elite Controllers.","volume":"10","author":"C Phetsouphanh","year":"2019","journal-title":"Front Immunol."},{"issue":"15","key":"ppat.1011725.ref054","doi-asserted-by":"crossref","first-page":"7494","DOI":"10.1128\/JVI.00438-15","article-title":"Cooperativity of HIV-Specific Cytolytic CD4 T Cells and CD8 T Cells in Control of HIV Viremia","volume":"89","author":"S Johnson","year":"2015","journal-title":"J Virol"},{"key":"ppat.1011725.ref055","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1186\/1742-4690-9-91","article-title":"CD8+ and CD4+ cytotoxic T cell escape mutations precede breakthrough SIVmac239 viremia in an elite controller.","volume":"9","author":"BJ Burwitz","year":"2012","journal-title":"Retrovirology."},{"issue":"8","key":"ppat.1011725.ref056","doi-asserted-by":"crossref","first-page":"e1005111","DOI":"10.1371\/journal.ppat.1005111","article-title":"HLA Class-II Associated HIV Polymorphisms Predict Escape from CD4+","volume":"11","author":"N Erdmann","year":"2015","journal-title":"T Cell Responses. PLoS Pathog"},{"key":"ppat.1011725.ref057","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1186\/s12935-020-01605-0","article-title":"CD137 agonist induces gastric cancer cell apoptosis by enhancing the functions of CD8(+) T cells via NF-kappaB signaling.","volume":"20","author":"BS Hu","year":"2020","journal-title":"Cancer Cell Int."},{"issue":"Suppl 3","key":"ppat.1011725.ref058","first-page":"e000733","article-title":"New emerging targets in cancer immunotherapy: CD137\/4-1BB costimulatory axis.","volume":"4","author":"I Etxeberria","year":"2020","journal-title":"ESMO Open."},{"issue":"12","key":"ppat.1011725.ref059","doi-asserted-by":"crossref","first-page":"3352","DOI":"10.1002\/eji.200636746","article-title":"CXCR5+ CCR7- CD8 T cells are early effector memory cells that infiltrate tonsil B cell follicles","volume":"37","author":"MF Quigley","year":"2007","journal-title":"Eur J Immunol"},{"issue":"12","key":"ppat.1011725.ref060","doi-asserted-by":"crossref","first-page":"965","DOI":"10.1016\/j.it.2018.10.002","article-title":"A Portrait of CXCR5(+) Follicular Cytotoxic CD8(+) T cells.","volume":"39","author":"D Yu","year":"2018","journal-title":"Trends Immunol"},{"issue":"7620","key":"ppat.1011725.ref061","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1038\/nature19317","article-title":"Follicular CXCR5- expressing CD8(+) T cells curtail chronic viral infection.","volume":"537","author":"R He","year":"2016","journal-title":"Nature"},{"issue":"7620","key":"ppat.1011725.ref062","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1038\/nature19330","article-title":"Defining CD8+ T cells that provide the proliferative burst after PD-1 therapy","volume":"537","author":"SJ Im","year":"2016","journal-title":"Nature"},{"key":"ppat.1011725.ref063","first-page":"8","article-title":"Cytolytic CD8(+) T cells infiltrate germinal centers to limit ongoing HIV replication in spontaneous controller lymph nodes.","author":"DR Collins","year":"2023","journal-title":"Sci Immunol."},{"issue":"4","key":"ppat.1011725.ref064","first-page":"407","article-title":"HIV and Cardiovascular Disease: From Insights to Interventions.","volume":"29","author":"MJ Feinstein","year":"2021","journal-title":"Top Antivir Med."},{"issue":"4 Suppl 3","key":"ppat.1011725.ref065","doi-asserted-by":"crossref","first-page":"19542","DOI":"10.7448\/IAS.17.4.19542","article-title":"Rates of cardiovascular events and deaths are associated with advanced stages of HIV-infection: results of the HIV HEART study 7, 5 year follow-up.","volume":"17","author":"S Esser","year":"2014","journal-title":"J Int AIDS Soc."},{"issue":"11","key":"ppat.1011725.ref066","first-page":"879","article-title":"Atherosclerosis in HIV-positive patients","volume":"91","author":"T Neumann","year":"2002"},{"key":"ppat.1011725.ref067","first-page":"19","article-title":"Cytotoxic CD4 T Cells-Friend or Foe during Viral Infection?","volume":"8","author":"JA Juno","year":"2017","journal-title":"Front Immunol."},{"issue":"3","key":"ppat.1011725.ref068","doi-asserted-by":"crossref","first-page":"e1008340","DOI":"10.1371\/journal.ppat.1008340","article-title":"Combination immunotherapy with anti-PD-L1 antibody and depletion of regulatory T cells during acute viral infections results in improved virus control but lethal immunopathology.","volume":"16","author":"P David","year":"2020","journal-title":"PLoS Pathog.PubMed Central PMCID"},{"issue":"6","key":"ppat.1011725.ref069","doi-asserted-by":"crossref","first-page":"1037","DOI":"10.1136\/annrheumdis-2011-201270","article-title":"Anti-TNF treatment blocks the induction of T cell-dependent humoral responses","volume":"72","author":"GF Salinas","year":"2013","journal-title":"Ann Rheum Dis"},{"issue":"41","key":"ppat.1011725.ref070","doi-asserted-by":"crossref","first-page":"5464","DOI":"10.1016\/j.vaccine.2015.08.011","article-title":"Immunosuppressive drugs impairs antibody response of the polysaccharide and conjugated pneumococcal vaccines in patients with Crohn\u2019s disease","volume":"33","author":"B Kantso","year":"2015","journal-title":"Vaccine"},{"issue":"11","key":"ppat.1011725.ref071","doi-asserted-by":"crossref","first-page":"1591","DOI":"10.1111\/jgh.13001","article-title":"Treatment with infliximab or azathioprine negatively impact the efficacy of hepatitis B vaccine in inflammatory bowel disease patients","volume":"30","author":"P Andrade","year":"2015","journal-title":"J Gastroenterol Hepatol"},{"issue":"13","key":"ppat.1011725.ref072","doi-asserted-by":"crossref","first-page":"3367","DOI":"10.1016\/j.celrep.2018.08.075","article-title":"Affinity Maturation Is Impaired by Natural Killer Cell Suppression of Germinal Centers.","volume":"24","author":"CE Rydyznski","year":"2018","journal-title":"Cell Rep"},{"issue":"11","key":"ppat.1011725.ref073","doi-asserted-by":"crossref","first-page":"4629","DOI":"10.1172\/JCI126714","article-title":"HIV-1 in lymph nodes is maintained by cellular proliferation during antiretroviral therapy","volume":"129","author":"WR McManus","year":"2019","journal-title":"J Clin Invest"},{"key":"ppat.1011725.ref074","doi-asserted-by":"crossref","first-page":"945956","DOI":"10.3389\/fcimb.2022.945956","article-title":"The reservoir of latent HIV","volume":"12","author":"J Chen","year":"2022","journal-title":"Front Cell Infect Microbiol"},{"key":"ppat.1011725.ref075","doi-asserted-by":"crossref","first-page":"3060","DOI":"10.3389\/fmicb.2019.03060","article-title":"Current Status of Latency Reversing Agents Facing the Heterogeneity of HIV-1 Cellular and Tissue Reservoirs.","volume":"10","author":"A Ait-Ammar","year":"2019","journal-title":"Front Microbiol."},{"key":"ppat.1011725.ref076","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1186\/1471-2172-9-13","article-title":"Coexpression of GM-CSF and antigen in DNA prime-adenoviral vector boost immunization enhances polyfunctional CD8+ T cell responses, whereas expression of GM-CSF antigen fusion protein induces autoimmunity","volume":"9","author":"M Tenbusch","year":"2008","journal-title":"BMC Immunol"},{"issue":"5","key":"ppat.1011725.ref077","doi-asserted-by":"crossref","first-page":"2225","DOI":"10.1128\/jvi.76.5.2225-2232.2002","article-title":"Temporal effects of gamma interferon deficiency on the course of Friend retrovirus infection in mice","volume":"76","author":"IM Stromnes","year":"2002","journal-title":"J Virol"},{"issue":"1","key":"ppat.1011725.ref078","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1016\/0042-6822(85)90187-4","article-title":"Use of a focal immunofluorescence assay on live cells for quantitation of retroviruses: distinction of host range classes in virus mixtures and biological cloning of dual-tropic murine leukemia viruses","volume":"141","author":"M Sitbon","year":"1985","journal-title":"Virology"},{"issue":"11","key":"ppat.1011725.ref079","doi-asserted-by":"crossref","first-page":"1709","DOI":"10.1038\/nprot.2015.085","article-title":"Advanced CUBIC protocols for whole-brain and whole-body clearing and imaging.","volume":"10","author":"EA Susaki","year":"2015","journal-title":"Nat Protoc."},{"key":"ppat.1011725.ref080","doi-asserted-by":"crossref","first-page":"936918","DOI":"10.3389\/fimmu.2022.936918","article-title":"Distinct Type I Interferon Subtypes Differentially Stimulate T Cell Responses in HIV-1-Infected Individuals.","volume":"13","author":"Z Karakoese","year":"2022","journal-title":"Front Immunol."},{"issue":"12","key":"ppat.1011725.ref081","doi-asserted-by":"crossref","first-page":"4425","DOI":"10.1182\/blood.V89.12.4425","article-title":"Tumor dormancy and cell signaling. V. Regrowth of the BCL1 tumor after dormancy is established","volume":"89","author":"ES Vitetta","year":"1997","journal-title":"Blood"}],"container-title":["PLOS Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.ppat.1011725","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,12,24]],"date-time":"2023-12-24T20:11:52Z","timestamp":1703448712000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.ppat.1011725"}},"subtitle":[],"editor":[{"given":"Daniel C.","family":"Douek","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2023,10,26]]},"references-count":81,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2023,10,26]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.ppat.1011725","relation":{},"ISSN":["1553-7374"],"issn-type":[{"value":"1553-7374","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,10,26]]}}}