{"doi":"10.3390/cancers15113046","title":"Follicular Helper and Regulatory T Cells Drive the Development of Spontaneous Epstein–Barr Virus Lymphoproliferative Disorder","abstract":"Epstein-Barr virus (EBV) is a ubiquitous herpes virus associated with various cancers. EBV establishes latency with life-long persistence in memory B-cells and can reactivate lytic infection placing immunocompromised individuals at risk for EBV-driven lymphoproliferative disorders (EBV-LPD). Despite the ubiquity of EBV, only a small percentage of immunocompromised patients (~20%) develop EBV-LPD. Engraftment of immunodeficient mice with peripheral blood mononuclear cells (PBMCs) from healthy EBV-seropositive donors leads to spontaneous, malignant, human B-cell EBV-LPD. Only about 20% of EBV+ donors induce EBV-LPD in 100% of engrafted mice (High-Incidence, HI), while another 20% of donors never generate EBV-LPD (No-Incidence, NI). Here, we report HI donors to have significantly higher basal T follicular helper (Tfh) and regulatory T-cells (Treg), and depletion of these subsets prevents/delays EBV-LPD. Transcriptomic analysis of CD4+ T cells from ex vivo HI donor PBMC revealed amplified cytokine and inflammatory gene signatures. HI vs. NI donors showed a marked reduction in IFNγ production to EBV latent and lytic antigen stimulation. In addition, we observed abundant myeloid-derived suppressor cells in HI donor PBMC that decreased CTL proliferation in co-cultures with autologous EBV+ lymphoblasts. Our findings identify potential biomarkers that may identify individuals at risk for EBV-LPD and suggest possible strategies for prevention.","journal":"Cancers","year":2023,"id":351237,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":9,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.952,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1096365,"name":"Mark Lustberg","orcid":null,"position":1,"is_corresponding":false},{"id":777734,"name":"Claire Hale","orcid":null,"position":2,"is_corresponding":false},{"id":410138,"name":"Shelby Sloan","orcid":"0000-0001-7366-9184","position":3,"is_corresponding":false},{"id":777215,"name":"Charlene Mao","orcid":"0000-0002-5517-7183","position":4,"is_corresponding":false},{"id":386160,"name":"Xiaoli Zhang","orcid":"0000-0002-2495-4568","position":5,"is_corresponding":false},{"id":366597,"name":"Hatice Gülçin Özer","orcid":"0000-0002-8315-8051","position":6,"is_corresponding":false},{"id":775563,"name":"Sarah Schlotter","orcid":null,"position":7,"is_corresponding":false},{"id":1096366,"name":"Porsha L. 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Ibrahim","orcid":"0000-0003-2242-2143","position":17,"is_corresponding":false},{"id":410149,"name":"Lapo Alinari","orcid":"0000-0002-8870-4162","position":18,"is_corresponding":false},{"id":471454,"name":"Gregory K. Behbehani","orcid":"0000-0002-9493-3607","position":19,"is_corresponding":false},{"id":309100,"name":"Polina Shindiapina","orcid":"0000-0001-6543-0050","position":20,"is_corresponding":false},{"id":3645,"name":"Michael A. Caligiuri","orcid":"0000-0002-4095-3020","position":21,"is_corresponding":false},{"id":308656,"name":"Robert A. Baiocchi","orcid":"0000-0002-1619-4853","position":22,"is_corresponding":false},{"id":309101,"name":"Elshafa H. 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