HLA-DR Expression Level in CD8+ T Cells Correlates With the Severity of Children With Acute Infectious Mononucleosis

Abstract

Background: This 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).

Methods: Twenty-eight pediatric patients with IM aged 3-8 years were enrolled. The immune phenotypes and cytokine secretion capability of T cells were detected.

Results: The percentages and absolute numbers of CD3⁺ and CD8⁺ T cells were significantly increased in IM patients compared with HCs. The percentages of Naïve 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-αβ, 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-γ, IL-2, and TNF-α) 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.

Conclusion: Robust 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.

Keywords: CD4+ T cells; CD8+ T cells; EBV; HLA-DR+ CD8+ T cells; infectious mononucleosis.