免疫学
爱泼斯坦-巴尔病毒
溶解循环
病毒
外周血单个核细胞
生物
病毒学
埃利斯波特
淋巴增殖性病變
医学
T细胞
免疫系统
淋巴瘤
体外
生物化学
作者
Elshafa H. Ahmed,Mark Lustberg,C. J. Hale,Shelby Sloan,Charlene Mao,Xiaoli Zhang,Hatice Gulcin Ozer,Sarah Schlotter,Porsha L. Smith,Frankie Jeney,Wing Keung Chan,Bonnie K. Harrington,Christoph Weigel,Eric Brooks,Haley L. Klimaszewski,Christopher C. Oakes,Tamrat Abebe,Muntaser E. Ibrahim,Lapo Alinari,Gregory K. Behbehani,Polina Shindiapina,Michael A. Caligiuri,Robert A. Baiocchi
出处
期刊:Cancers
[MDPI AG]
日期:2023-06-03
卷期号:15 (11): 3046-3046
被引量:1
标识
DOI:10.3390/cancers15113046
摘要
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.
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