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Updated: Sep 5, 2026
Separation of Immune Cell Subpopulations in Peripheral Blood Samples from Children with Infectious Mononucleosis
Published on: September 7, 2022
Ectopic Epstein-Barr virus infection in T cells identifies reduced therapeutic responsiveness and immune dysfunction
Zhifan Zhao1, Zhuojun Liu1, Qiang Huang2
1Peking University People's Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Cell and Gene Therapy for Hematologic Malignancies, Peking University, Beijing, China.
Objectives:
Epstein-Barr virus (EBV) reactivation after allogeneic haematopoietic stem cell transplantation (allo-HSCT) is typically monitored by plasma viral load, but this fails to capture cellular reservoirs. Lineage-specific testing, although usually performed in high-risk patients, may identify biologically distinct disease states. We aimed to evaluate the clinical and biological significance of lineage-specific EBV quantification especially ectopic EBV infection in T cells in allo-HSCT recipients with EBV reactivation.
Methods:
We analysed 144 allo-HSCT recipients with EBV reactivation who underwent lineage-specific EBV quantification, assessed whether T-cell tropic EBV burden identifies a phenotype with reduced responsiveness to rituximab therapy, an increased risk of posttransplant lymphoproliferative disorder (PTLD), and specific features of underlying immune dysfunction.
Results:
Among the tested high-risk patients with high EBV loads and clinical symptoms, 66.6% exhibited T-cell tropic EBV infection. Compared with non-T-cell tropic infection, T-cell tropism was associated with higher rituximab courses and lower complete response rates (67% vs. 81%, p 0.029), suggesting insufficient efficacy of CD20-directed therapy. Patients with T-cell tropic infection had a significantly higher 1-year cumulative incidence of PTLD compared with the non-T-cell tropic group (77% vs. 41.6%; p <0.001). Single-cell RNA sequencing and mass cytometry analyses revealed an exhausted T-cell phenotype with diminished stemness in T-cell tropic EBV-infected patients.
Conclusions:
These findings suggest that T-cell EBV quantification distinguishes a therapeutically challenging subtype of EBV reactivation characterized by immune dysfunction and reduced responsiveness to rituximab-based therapy. Incorporating assessment of cellular viral reservoirs into posttransplant EBV monitoring strategies may facilitate early risk stratification and support timely therapeutic escalation beyond rituximab alone.
