Characteristics of immunological events in Epstein-Barr virus infection in children with infectious mononucleosis

Backgrounds & aimsEpstein-Barr virus (EBV) infection occurs commonly in children and may cause acute infectious mononucleosis (AIM) and various malignant diseases. Host immune responses are key players in the resistance to EBV infection. We here assessed the immunological events and laborato...

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Main Authors: Yunyun Zhang, Chengrong Huang, Hao Zhang, Zhi Duan, Qian Liu, Jianfei Li, Qiyin Zong, Yu Wei, Futing Liu, Wanlu Duan, Liwen Chen, Qiang Zhou, Qin Wang
Format: Article
Language:English
Published: Frontiers Media S.A. 2023-02-01
Series:Frontiers in Pediatrics
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fped.2023.1060053/full
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author Yunyun Zhang
Chengrong Huang
Chengrong Huang
Hao Zhang
Zhi Duan
Qian Liu
Jianfei Li
Qiyin Zong
Yu Wei
Futing Liu
Wanlu Duan
Liwen Chen
Qiang Zhou
Qin Wang
author_facet Yunyun Zhang
Chengrong Huang
Chengrong Huang
Hao Zhang
Zhi Duan
Qian Liu
Jianfei Li
Qiyin Zong
Yu Wei
Futing Liu
Wanlu Duan
Liwen Chen
Qiang Zhou
Qin Wang
author_sort Yunyun Zhang
collection DOAJ
description Backgrounds & aimsEpstein-Barr virus (EBV) infection occurs commonly in children and may cause acute infectious mononucleosis (AIM) and various malignant diseases. Host immune responses are key players in the resistance to EBV infection. We here assessed the immunological events and laboratory indicators of EBV infection, as well as determined the clinical usefulness of evaluating the severity and efficacy of antiviral therapy in AIM patients.MethodsWe enrolled 88 children with EBV infection. The immune environment was defined by immunological events such as frequencies of lymphocyte subsets, phenotypes of T cells, and their ability to secrete cytokines, and so on. This environment was analyzed in EBV-infected children with different viral loads and in children in different phases of infectious mononucleosis (IM) from disease onset to convalescence.ResultsChildren with AIM had higher frequencies of CD3+ T and CD8+ T cells, but lower frequencies of CD4+ T cells and CD19+ B cells. In these children, the expression of CD62L was lower and that of CTLA-4 and PD-1 was higher on T cells. EBV exposure induced granzyme B expression, but reduced IFN-γ secretion, by CD8+ T cells, whereas NK cells exhibited reduced granzyme B expression and increased IFN-γ secretion. The frequency of CD8+ T cells was positively correlated with the EBV DNA load, whereas the frequencies of CD4+ T cells and B cells were negatively correlated. During the convalescent phase of IM, CD8+ T cell frequency and CD62L expression on T cells were restored. Moreover, patient serum levels of IL-4, IL-6, IL-10, and IFN-γ were considerably lower throughout the convalescent phase than throughout the acute phase.ConclusionRobust expansion of CD8+ T cells, accompanied by CD62L downregulation, PD-1 and CTLA-4 upregulation on T cells, enhanced granzyme B production, and impaired IFN-γ secretion, is a typical characteristic of immunological events in children with AIM. Noncytolytic and cytolytic effector functions of CD8+ T cells are regulated in an oscillatory manner. Furthermore, the AST level, number of CD8+ T cells, and CD62L expression on T cells may act as markers related to IM severity and the effectiveness of antiviral treatment.
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spelling doaj.art-951cdb511c6d435988e5c7a779f4d5da2023-02-09T09:50:15ZengFrontiers Media S.A.Frontiers in Pediatrics2296-23602023-02-011110.3389/fped.2023.10600531060053Characteristics of immunological events in Epstein-Barr virus infection in children with infectious mononucleosisYunyun Zhang0Chengrong Huang1Chengrong Huang2Hao Zhang3Zhi Duan4Qian Liu5Jianfei Li6Qiyin Zong7Yu Wei8Futing Liu9Wanlu Duan10Liwen Chen11Qiang Zhou12Qin Wang13Department of Clinical Laboratory, The Second Hospital of Anhui Medical University, Hefei, ChinaDepartment of Clinical Laboratory, The Second Hospital of Anhui Medical University, Hefei, ChinaDepartment of Clinical Laboratory, Anqing Municipal Hospital, Anqing, ChinaDepartment of Clinical Laboratory, The Second Hospital of Anhui Medical University, Hefei, ChinaDepartment of Clinical Laboratory, The Second Hospital of Anhui Medical University, Hefei, ChinaDepartment of Clinical Laboratory, The Second Hospital of Anhui Medical University, Hefei, ChinaDepartment of Clinical Laboratory, The Second Hospital of Anhui Medical University, Hefei, ChinaDepartment of Clinical Laboratory, The Second Hospital of Anhui Medical University, Hefei, ChinaDepartment of Clinical Laboratory, The Second Hospital of Anhui Medical University, Hefei, ChinaDepartment of Clinical Laboratory, The Second Hospital of Anhui Medical University, Hefei, ChinaDepartment of Clinical Laboratory, The Second Hospital of Anhui Medical University, Hefei, ChinaDepartment of Clinical Laboratory, The Second Hospital of Anhui Medical University, Hefei, ChinaDepartment of Clinical Laboratory, The Second Hospital of Anhui Medical University, Hefei, ChinaDepartment of Clinical Laboratory, The Second Hospital of Anhui Medical University, Hefei, ChinaBackgrounds & aimsEpstein-Barr virus (EBV) infection occurs commonly in children and may cause acute infectious mononucleosis (AIM) and various malignant diseases. Host immune responses are key players in the resistance to EBV infection. We here assessed the immunological events and laboratory indicators of EBV infection, as well as determined the clinical usefulness of evaluating the severity and efficacy of antiviral therapy in AIM patients.MethodsWe enrolled 88 children with EBV infection. The immune environment was defined by immunological events such as frequencies of lymphocyte subsets, phenotypes of T cells, and their ability to secrete cytokines, and so on. This environment was analyzed in EBV-infected children with different viral loads and in children in different phases of infectious mononucleosis (IM) from disease onset to convalescence.ResultsChildren with AIM had higher frequencies of CD3+ T and CD8+ T cells, but lower frequencies of CD4+ T cells and CD19+ B cells. In these children, the expression of CD62L was lower and that of CTLA-4 and PD-1 was higher on T cells. EBV exposure induced granzyme B expression, but reduced IFN-γ secretion, by CD8+ T cells, whereas NK cells exhibited reduced granzyme B expression and increased IFN-γ secretion. The frequency of CD8+ T cells was positively correlated with the EBV DNA load, whereas the frequencies of CD4+ T cells and B cells were negatively correlated. During the convalescent phase of IM, CD8+ T cell frequency and CD62L expression on T cells were restored. Moreover, patient serum levels of IL-4, IL-6, IL-10, and IFN-γ were considerably lower throughout the convalescent phase than throughout the acute phase.ConclusionRobust expansion of CD8+ T cells, accompanied by CD62L downregulation, PD-1 and CTLA-4 upregulation on T cells, enhanced granzyme B production, and impaired IFN-γ secretion, is a typical characteristic of immunological events in children with AIM. Noncytolytic and cytolytic effector functions of CD8+ T cells are regulated in an oscillatory manner. Furthermore, the AST level, number of CD8+ T cells, and CD62L expression on T cells may act as markers related to IM severity and the effectiveness of antiviral treatment.https://www.frontiersin.org/articles/10.3389/fped.2023.1060053/fullimmunological eventsEpstein-Barr virus infectioninfectious mononucleosischildrenlymphocytes
spellingShingle Yunyun Zhang
Chengrong Huang
Chengrong Huang
Hao Zhang
Zhi Duan
Qian Liu
Jianfei Li
Qiyin Zong
Yu Wei
Futing Liu
Wanlu Duan
Liwen Chen
Qiang Zhou
Qin Wang
Characteristics of immunological events in Epstein-Barr virus infection in children with infectious mononucleosis
Frontiers in Pediatrics
immunological events
Epstein-Barr virus infection
infectious mononucleosis
children
lymphocytes
title Characteristics of immunological events in Epstein-Barr virus infection in children with infectious mononucleosis
title_full Characteristics of immunological events in Epstein-Barr virus infection in children with infectious mononucleosis
title_fullStr Characteristics of immunological events in Epstein-Barr virus infection in children with infectious mononucleosis
title_full_unstemmed Characteristics of immunological events in Epstein-Barr virus infection in children with infectious mononucleosis
title_short Characteristics of immunological events in Epstein-Barr virus infection in children with infectious mononucleosis
title_sort characteristics of immunological events in epstein barr virus infection in children with infectious mononucleosis
topic immunological events
Epstein-Barr virus infection
infectious mononucleosis
children
lymphocytes
url https://www.frontiersin.org/articles/10.3389/fped.2023.1060053/full
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