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Epstein-Barr virus-specific T-cell response in pediatric liver transplant recipients: a cross-sectional study by
Ricardo Cuesta-Martín de la Cámara1,2,3, Andrea Torices-Pajares2, Laura Miguel-Berenguel1
1Clinical Immunology Department, University Hospital La Paz, Madrid, Spain.
Insights
Measuring Epstein-Barr virus (EBV) T-cell responses helps manage immunosuppression in pediatric liver transplant patients. Increased polyfunctional CD8+ T cells indicate EBV contact, especially with viral load positivity.
Area of Science:
- Immunology
- Virology
- Transplantation
Background:
- Epstein-Barr virus (EBV) infections pose risks in immunosuppressed transplant recipients.
- Monitoring EBV-specific T-cell responses can guide immunosuppression adjustments.
- Pediatric liver transplant patients with persistent EBV infections require careful management.
Purpose of the Study:
- To define and characterize T-cell responses against EBV in pediatric liver-transplant patients.
- To correlate EBV-specific T-cell profiles with serological and viral load status.
- To assess the utility of T-cell response measurement for managing EBV in this cohort.
Main Methods:
- Cross-sectional study of 38 immunosuppressed pediatric liver-transplant patients and 25 healthy adult controls.
- Categorization of patients based on EBV serological and viral load status.
- Assessment of T-cell response via EBV peptide stimulation, intracellular cytokine staining, and activation-induced marker analysis.
Main Results:
- Polyfunctional CD8+ T cells were indicative of previous EBV contact.
- An increased polyfunctional CD8+CD107a+IFNɣ+IL2-TNFα- profile was observed in serology-positive and viral-load positive patients.
- Central memory T cells were more prevalent in EBV-seropositive adults, suggesting prior exposure.
Conclusions:
- Polyfunctional CD8+ T-cell responses effectively detect prior EBV contact in pediatric liver transplant recipients.
- Elevated CD8+CD107a+IFNɣ+IL2-TNFα- T cells correlate with positive EBV viral loads.
- Central memory CD4+ T cells are a more sensitive indicator of prior EBV exposure in adults.
Background:
Epstein-Barr virus (EBV) specific T-cell response measurement can help adjust immunosuppression in transplant patients with persistent infections. We aim to define T-cell responses against EBV in a cohort of pediatric liver-transplant patients.
Methods:
Thirty-eight immunosuppressed pediatric liver-transplant patients (IP) and 25 EBV-seropositive healthy-adult controls (HC) were included in our cross-sectional study. Based on their EBV serological (S) and viral load (VL) status, patients were categorized into IP-SNEG, IP-SPOSVLNEG and IP-SPOSVLPOS groups. T-cell response was assessed at two timepoints by stimulating cells with EBV peptides (PepTivator®) and performing intracellular-cytokine and activation-induced marker staining. Background subtraction was used to determine EBV-specific T-lymphocyte frequency.
Results:
Polyfunctional CD8+ T cells indicated previous EBV contact (IP-SNEG 0.00% vs IP-SPOS 0.04% and HC 0.02%; p=0.001 and p=0.01, respectively). Polyfunctional CD8+CD107a+IFNɣ+IL2-TNFα- profile was increased in serology-positive (IP-SNEG 0.01% vs IP-SPOS 0.13% and HC 0.03%; p=0.01 and p=0.50, respectively) and viral-load positive (IP-SPOSVLPOS 0.43% vs IP-SPOSVLNEG 0.07% and HC 0.03%; p=0.03 and p=0.001, respectively) patients. Central-memory cells were increased among serology-positive adults (IP-SNEG 0.00% vs IP-SPOS 0.13% and HC 4.33%; p=0.58 and p=0.002, respectively). At the second timepoint, IP-SNEG patients remained negative (first visit 0.01% vs second visit 0.00%, p=0.44). On the other hand, IP-SPOSVLPOS patients had cleared viral loads and, subsequently, decreased polyfunctional CD8+CD107a+IFNɣ+IL2-TNFα- cells (first visit 0.43% vs second visit 0.10%, p=0.81).
Conclusion:
Polyfunctional CD8+ EBV-specific T-cell response allows detecting EBV previous contact in liver-transplant children. %CD8+CD107a+IFNɣ+IL2-TNFα- is increased in patients with positive viral loads. Central memory CD4+ T-cell population more effectively determines prior EBV-exposure in adults.
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