BackgroundThis study aimed to assess the host immune signatures associated with EBV infection and its clinical value in indicating the severity of children with acute infectious mononucleosis (IM). MethodsTwenty-eight pediatric patients with IM aged 3-8 years were enrolled. The immune phenotypes and cytokine secretion capability of T cells were detected. ResultsThe percentages and absolute numbers of CD3(+) and CD8(+) T cells were significantly increased in IM patients compared with HCs. The percentages of Naive CD4(+) and CD8(+) T cells were decreased but with increased percentages of memory CD4(+) and CD8(+) T subsets. Our results showed the upregulation of active marker HLA-DR, TCR-alpha beta, and inhibitory receptors PD-1, TIGIT in CD8(+) T cells from IM patients, which suggested that effective cytotoxic T cells were highly against EBV infection. However, EBV exposure impaired the cytokine (IFN-gamma, IL-2, and TNF-alpha) secretion capability of CD4(+) and CD8(+) T cells after stimulation with PMA/ionomycin in vitro. Multivariate analysis revealed that the percentage of HLA-DR+ CD8(+) T cells was an independent prognostic marker for IM. The percentage of HLA-DR+ CD8(+) T cells was significantly correlated with high viral load and abnormal liver function results. ConclusionRobust expansion and upregulation of HLA-DR in CD8(+) T cells, accompanied with impaired cytokine secretion, were typical characteristics of children with acute IM. The percentage of HLA-DR+ CD8(+) T cells might be used as a prominent marker not only for the early diagnosis but also for indicating the severity of IM.