Original Articles
Vol. 16 No. 1 (2024): Review Articles, Original Article, Scientific Letter, Case Reports Letter to the Editor
LYMPHOCYTES IN PATIENTS WITH CHRONIC ACTIVE EPSTEIN-BARR VIRUS INFECTION EXHIBITED ELEVATED PD-1/PD-L1 EXPRESSION AND A PREVAILING TH2 IMMUNE RESPONSE.
EPSTEIN-BARR VIRUS INFECTION EXHIBITED ELEVATED PD-1/PD-L1
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All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
Received: November 12, 2023
Accepted: March 18, 2024
Accepted: March 18, 2024
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Background And Objectives: Chronic active Epstein-Barr virus infection (CAEBV) is a lymphoproliferative disorder characterized by the increased numbers of EBV-infected T/natural killer (NK) cells and ongoing symptoms resembling infectious mononucleosis. Nonetheless, the exact correlation between peripheral lymphocyte subsets and the development of CAEBV remains uncertain. Methods: Consequently, we examined the levels of programmed cell death 1 (PD-1)/programmed death ligand 1 (PD-L1) expression, the status of EBV infection, and the frequencies of peripheral lymphocyte subpopulations in 24 patients with CAEBV and 15 EBV-seronegative donors using flow cytometry.
Results: Patients with CAEBV showed a notable rise in the expression levels of PD-1 and PD-L1 in peripheral T and NK cells compared to healthy donors (P < 0.05). The induction of PD-L1 expression was attributed to EBV infection. Moreover, most of the T cells infected with EBV displayed a memory phenotype characterized by the presence of CD45RO+. Additionally, patients with CAEBV showed markedly decreased frequency of helper T cells 1 (Th1) and naïve T (Tn) cells, and significantly elevated frequency of Th2 and effector-memory T (Tem) cells.
Conclusions: To summarize, EBV might evade the immune system by inducing PD-1/PD-L1 expression in peripheral T and NK cells, and promoting Th2 immune response dominance. Additionally, it may establish long-term persistence by infecting memory T cells in CAEBV.
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Citations
Okuno Y, Murata T, Sato Y, et al. Defective Epstein–Barr virus in chronic active infection and haematological malignancy. Nat Microbiol. 2019; 4(3): 404-413.
PMid: 30664667
Chakravorty S, Afzali B, Kazemian M. EBV-associated diseases: Current therapeutics and emerging technologies. Front Immunol. 2022; 13:1059133.
PMid:36389670
Cui X, Snapper CM. Epstein Barr Virus: Development of Vaccines and Immune Cell Therapy for EBV-Associated Diseases. Front Immunol. 2021; 12:734471.
PMid: 34691042
Leticia QM, Steven HS, Thomas T, et al. New concepts in EBV-associated B, T, and NK cell lymphoproliferative disorders. Virchows Arch. 2023; 482(1): 227-244.
PMid: 36216980
Elias C, Elaine SJ, James RC, et al. The International Consensus Classification of Mature Lymphoid Neoplasms: a report from the Clinical Advisory Committee. Blood. 2022;140(11):1229-1253.
PMid: 35653592
Yonese I, Sakashita C, Imadome KI, et al. Nationwide survey of systemic chronic active EBV infection in Japan in accordance with the new WHO classification. Blood Adv. 2020; 4(13): 2918-2926.
PMid: 32598475
Austen JJW, Charlotte JH, Claire B. Severe Epstein-Barr virus infection in primary immunodeficiency and the normal host. Br J Haematol. 2016;175(4): 559-576.
PMid: 27748521
Jiancheng L, Xiaokang C, Haiming W, et al. Peripheral blood lymphocyte counts in patients with infectious mononucleosis or chronic active Epstein-Barr virus infection and prognostic risk factors of chronic active Epstein-Barr virus infection. Am J Transl Res. 2021; 13 (11): 12797-12806.
PMid: 34956494
Ming Y, Dechao J, Hanxiao X, et al. Biomarkers for predicting efficacy of PD-1/PD-L1 inhibitors. Mol Cancer. 2018;17(1):129-143.
PMid: 30139382
Xi-Wen B, Hua W, Wen-Wen Z, et al. PD-L1 is upregulated by EBV-driven LMP1 through NF-κB pathway and correlates with poor prognosis in natural killer/T-cell lymphoma. J Hematol Oncol. 2016; 9(1):109-121.
PMid: 27737703
Jie W, Junshang G, Yian W, et al. EBV miRNAs BART11 and BART17-3p promote immune escape through the enhancer-mediated transcription of PD-L1. Nat Commun. 2022;13(1):866-885.
PMid: 35165282
Junshang G, Jie W, Fang X, et al. Epstein-Barr Virus-Encoded Circular RNA CircBART2.2 Promotes Immune Escape of Nasopharyngeal Carcinoma by Regulating PD-L1. Cancer Res. 2021; 81(19):5074-5088.
PMid: 34321242
Yue S, Jingshi W, Yini W, et al. PD-1 blockade and lenalidomide combination therapy for chronic active Epstein-Barr virus infection. Clin Microbiol Infect. 2023; 29(6): e7-e13
PMid: 36702399
Sebastian FP, Oscar S, Yasodha N. Defining the elusive boundaries of chronic active Epstein-Barr virus infection. Haematologica. 2018; 103(6): 924-927.
PMid: 29866887
Benjamin F, David B, Julie B, et al. Rapid identification and characterization of infected cells in blood during chronic active Epstein-Barr virus infection. J Exp Med. 2020; 217(11): e20192262.
https://rupress.org/jem/article/217/11/e20192262/152032/Rapid-identification-and-characterization-of
PMid: 32812031
Ann WNA, Carey LS, Alyssa L, et al. Naïve CD4+ T Cell Lymphopenia and Apoptosis in Chronic Hepatitis C Virus Infection Is Driven by the CD31+ Subset and Is Partially Normalized in Direct-Acting Antiviral Treated Persons. Front Immunol. 2021; 12: 641230.
PMid: 33912168
Ann WNA, Carey LS, Lenche K, et al. Variable Normalization of Naïve CD4+ Lymphopenia and Markers of Monocyte and T Cell Activation over the Course of Direct-Acting Anti-Viral Treatment of Chronic Hepatitis C Virus Infection. Viruses. 2021; 14(1): 50-60.
PMid: 35062255
Poonam S, Bhagyashri T, Prachi A, et al. Lymphopenia with Altered T Cell Subsets in Hospitalized COVID-19 Patients in Pune, India. Viral Immunol. 2023; 36(3): 163-175.
PMid: 36897333
Quirin N, Marc S, Florian W, et al. Pro- and Anti-Inflammatory Responses in Severe COVID-19-Induced Acute Respiratory Distress Syndrome—An Observational Pilot Study. Front Immunol. 2020; 11: 581338.
PMid: 33123167
Zhanfeng L, Xue D, Zhaoqi Z, et al. Age‐related thymic involution: Mechanisms and functional impact. Aging Cell. 2022; 21(8): e13671.
PMid: 35822239
Hui S, Chen Y, Ya-Nan G, et al. Recirculating Th2 cells induce severe thymic dysfunction via IL-4/STAT6 signaling pathway. Biochem Biophys Res Commun. 2018; 501(1): 320-327.
PMid: 29738764
Francesco A, Chiara R, Sergio R. The 3 major types of innate and adaptive cell-mediated effector immunity. J Allergy Clin Immunol. 2015;135(3): 626-35.
PMid: 25528359
Weihang L, Jindong H, Weifang X, et al. Distinct spatial and temporal roles for Th1, Th2, and Th17 cells in asthma. Front Immunol. 2022; 13: 974066.
PMid: 36032162
Charles AD. The IL-1 family of cytokines and receptors in rheumatic diseases. Nat Rev Rheumatol. 2019;15(10): 612-632.
PMid: 31515542
Punniyakoti VT, Srinivasan R, Poojitha M, et al. Modulation of IL-33/ST2 signaling as a potential new therapeutic target for cardiovascular diseases. Cytokine Growth Factor Rev. 2023; 71-72: 94-104.
PMid: 37422366
Jochen S, Alexander O, Elizabeth O, et al. IL-33, an interleukin-1-like cytokine that signals via the IL-1 receptor-related protein ST2 and induces T helper type 2-associated cytokines. Immunity. 2005; 23(5): 479-90.
PMid: 16286016
Jaewoo H, Soohyun K, P CL. Interleukin-33 and ST2 Signaling in Tumor Microenvironment. J Interferon Cytokine Res. 2019; 39(1): 61-71.
PMid: 30256696
Corinne C, Jean-PG. Interleukin-33 (IL-33): A critical review of its biology and the mechanisms involved in its release as a potent extracellular cytokine. Cytokine. 2022; 156: 155891-155906.
PMid: 35640416
Wenyi J, Jingyao L, Ying Y, et al. IL‐33/ST2 as a potential target for tumor immunotherapy. Eur J Immunol. 2021; 51(8): 1943-1955.
PMid: 34131922
Siyan C, Luxi W, Lirong P, et al. Hepatitis B virus X protein (HBx) promotes ST2 expression by GATA2 in liver cells. Mol Immunol. 2020; 123: 32-39.
PMid: 32413787
Tiago LF, Andreas HG, Christian L, et al. Macrophage: A Potential Target on Cartilage Regeneration. Front Immunol. 2020; 11(11):111-120.
PMid: 32117263
Anna B, Slaven C, Valentina B, et al. IL-1 receptor blockade skews inflammation towards Th2 in a mouse model of systemic sclerosis. Eur Respir J. 2019; 54(3): 1900154-1900165.
PMid: 31320452
Carl RH, Bojana SM, Crissy F, et al. The role of Interleukin 1 receptor antagonist in mesenchymal stem cell‐based tissue repair and regeneration. Biofactors. 2020; 46(2): 263-275.
PMid: 31755595
Supporting Agencies
Key Scientific Project for Capital’s Health Development Research: 2020-1-2022;, National Natural Science Foundation of China: 82370185;, Beijing Municipal Science & Technology Commission: 7181003How to Cite
“LYMPHOCYTES IN PATIENTS WITH CHRONIC ACTIVE EPSTEIN-BARR VIRUS INFECTION EXHIBITED ELEVATED PD-1/PD-L1 EXPRESSION AND A PREVAILING TH2 IMMUNE RESPONSE.: EPSTEIN-BARR VIRUS INFECTION EXHIBITED ELEVATED PD-1/PD-L1” (2024) Mediterranean Journal of Hematology and Infectious Diseases, 16(1), p. e2024037. doi:10.4084/MJHID.2024.037.
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