Epstein-Barr virus-specific T-cell response in pediatric liver transplant recipients: a cross-sectional study by multiparametric flow cytometry.

Autor: Cuesta-Martín de la Cámara R; Clinical Immunology Department, University Hospital La Paz, Madrid, Spain.; Lymphocyte Pathophysiology in Immunodeficiencies Group, La Paz Institute for Health Research (IdiPAZ), Madrid, Spain.; Medicine and surgery Department, Autonomous University of Madrid, Madrid, Spain., Torices-Pajares A; Lymphocyte Pathophysiology in Immunodeficiencies Group, La Paz Institute for Health Research (IdiPAZ), Madrid, Spain., Miguel-Berenguel L; Clinical Immunology Department, University Hospital La Paz, Madrid, Spain., Reche-Yebra K; Lymphocyte Pathophysiology in Immunodeficiencies Group, La Paz Institute for Health Research (IdiPAZ), Madrid, Spain., Frauca-Remacha E; Paediatric Hepatology Department, University Hospital La Paz, Madrid, Spain.; European Reference Network (ERN) RARE LIVER, Madrid, Spain.; European Reference Network (ERN) TransplantChild, Madrid, Spain., Hierro-Llanillo L; Paediatric Hepatology Department, University Hospital La Paz, Madrid, Spain.; European Reference Network (ERN) RARE LIVER, Madrid, Spain.; European Reference Network (ERN) TransplantChild, Madrid, Spain., Muñoz-Bartolo G; Paediatric Hepatology Department, University Hospital La Paz, Madrid, Spain.; European Reference Network (ERN) RARE LIVER, Madrid, Spain.; European Reference Network (ERN) TransplantChild, Madrid, Spain., Lledín-Barbacho MD; Paediatric Hepatology Department, University Hospital La Paz, Madrid, Spain.; European Reference Network (ERN) RARE LIVER, Madrid, Spain.; European Reference Network (ERN) TransplantChild, Madrid, Spain., Gutiérrez-Arroyo A; Microbiology Department, University Hospital La Paz, Madrid, Spain., Martínez-Feito A; Clinical Immunology Department, University Hospital La Paz, Madrid, Spain., López-Granados E; Clinical Immunology Department, University Hospital La Paz, Madrid, Spain.; Lymphocyte Pathophysiology in Immunodeficiencies Group, La Paz Institute for Health Research (IdiPAZ), Madrid, Spain.; European Reference Network (ERN) TransplantChild, Madrid, Spain.; Centre for Biomedical Network Research on rare diseases (CIBERER U767), Madrid, Spain., Sánchez-Zapardiel E; Clinical Immunology Department, University Hospital La Paz, Madrid, Spain.; Lymphocyte Pathophysiology in Immunodeficiencies Group, La Paz Institute for Health Research (IdiPAZ), Madrid, Spain.; European Reference Network (ERN) TransplantChild, Madrid, Spain.
Jazyk: angličtina
Zdroj: Frontiers in immunology [Front Immunol] 2024 Oct 24; Vol. 15, pp. 1479472. Date of Electronic Publication: 2024 Oct 24 (Print Publication: 2024).
DOI: 10.3389/fimmu.2024.1479472
Abstrakt: 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-S NEG , IP-S POS VL NEG and IP-S POS VL POS 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-S NEG 0.00% vs IP-S POS 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-S NEG 0.01% vs IP-S POS 0.13% and HC 0.03%; p=0.01 and p=0.50, respectively) and viral-load positive (IP-S POS VL POS 0.43% vs IP-S POS VL NEG 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-S NEG 0.00% vs IP-S POS 0.13% and HC 4.33%; p=0.58 and p=0.002, respectively). At the second timepoint, IP-S NEG patients remained negative (first visit 0.01% vs second visit 0.00%, p=0.44). On the other hand, IP-S POS VL POS 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.
Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision.
(Copyright © 2024 Cuesta-Martín de la Cámara, Torices-Pajares, Miguel-Berenguel, Reche-Yebra, Frauca-Remacha, Hierro-Llanillo, Muñoz-Bartolo, Lledín-Barbacho, Gutiérrez-Arroyo, Martínez-Feito, López-Granados and Sánchez-Zapardiel.)
Databáze: MEDLINE
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