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

Abstract

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.

Distribution of Epstein–Barr Virus LMP1 Variants in Patients with Infectious Mononucleosis and Association with Selected Biochemical and Hematological Parameters

“…Studies on the molecular diversity of EBV in IM are of particular importance in the more detailed characterization of innate and specific immune responses to EBV, the fundamental immunobiology of EBV infection as well as in the development of prophylactic and therapeutic vaccines [ 50 , 51 , 52 ]. The recently described role of EBV as a co-factor in the development of multiple sclerosis has renewed the interest in the development of prophylactic based on mRNA technology [ 51 ].…”

Deciphering the Role of Epstein–Barr Virus Latent Membrane Protein 1 in Immune Modulation: A Multifaced Signalling Perspective

“…Furthermore, a study by Rajendran et al (2016) demonstrated that ectopic CD137 expression on HRS cells enables the secretion of IL-13, facilitating immune escape by reducing IFNγ [ 180 ]. Decreases in IFN- γ secretion by cytokoxic T lymphocytes were observed in a recent study by Zhang et al (2023) in children with infectious mononucleosis [ 181 ]. On the other hand, Lambert et al 2007 demonstrated for the first time that the induction of IL-10 by LMP1 in B cells is not only p38-dependent but also uses the PI3K/Akt pathway [ 84 ].…”

Liver injury and prolonged hospitalization as indicators of severity in patients with adenovirus infections

“…For severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) infection, severe cases more frequently had dyspnea, lymphopenia, and hypoalbuminemia, with higher levels of alanine aminotransferase(ALT), lactate dehydrogenase, C-reactive protein, ferritin, and D-dimer as well as markedly higher levels of IL-2R, IL-6, IL-10, and TNF-α [ 11 ]. For Epstein-Barr virus(EBV) infection, aspartate aminotransferase(AST) level, number of CD8 + T cells, and CD62L expression on T cells were related to the severity of infectious mononucleosis [ 12 ]. For ADV infection, more data on co-infection were reported, for example human ADV type 7 and invasive pulmonary fungal co-infection [ 13 ], mycoplasma pneumoniae(MP) and ADV co-infection [ 14 ] and so forth.…”