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

BackgroundEpstein-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.MethodsThirty-eight immunosuppressed pediatric...

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Main Authors: Ricardo Cuesta-Martín de la Cámara, Andrea Torices-Pajares, Laura Miguel-Berenguel, Keren Reche-Yebra, Esteban Frauca-Remacha, Loreto Hierro-Llanillo, Gema Muñoz-Bartolo, María Dolores Lledín-Barbacho, Almudena Gutiérrez-Arroyo, Ana Martínez-Feito, Eduardo López-Granados, Elena Sánchez-Zapardiel
Format: Article
Language:English
Published: Frontiers Media S.A. 2024-10-01
Series:Frontiers in Immunology
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Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2024.1479472/full
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author Ricardo Cuesta-Martín de la Cámara
Ricardo Cuesta-Martín de la Cámara
Ricardo Cuesta-Martín de la Cámara
Andrea Torices-Pajares
Laura Miguel-Berenguel
Keren Reche-Yebra
Esteban Frauca-Remacha
Esteban Frauca-Remacha
Esteban Frauca-Remacha
Loreto Hierro-Llanillo
Loreto Hierro-Llanillo
Loreto Hierro-Llanillo
Gema Muñoz-Bartolo
Gema Muñoz-Bartolo
Gema Muñoz-Bartolo
María Dolores Lledín-Barbacho
María Dolores Lledín-Barbacho
María Dolores Lledín-Barbacho
Almudena Gutiérrez-Arroyo
Ana Martínez-Feito
Eduardo López-Granados
Eduardo López-Granados
Eduardo López-Granados
Eduardo López-Granados
Elena Sánchez-Zapardiel
Elena Sánchez-Zapardiel
Elena Sánchez-Zapardiel
author_facet Ricardo Cuesta-Martín de la Cámara
Ricardo Cuesta-Martín de la Cámara
Ricardo Cuesta-Martín de la Cámara
Andrea Torices-Pajares
Laura Miguel-Berenguel
Keren Reche-Yebra
Esteban Frauca-Remacha
Esteban Frauca-Remacha
Esteban Frauca-Remacha
Loreto Hierro-Llanillo
Loreto Hierro-Llanillo
Loreto Hierro-Llanillo
Gema Muñoz-Bartolo
Gema Muñoz-Bartolo
Gema Muñoz-Bartolo
María Dolores Lledín-Barbacho
María Dolores Lledín-Barbacho
María Dolores Lledín-Barbacho
Almudena Gutiérrez-Arroyo
Ana Martínez-Feito
Eduardo López-Granados
Eduardo López-Granados
Eduardo López-Granados
Eduardo López-Granados
Elena Sánchez-Zapardiel
Elena Sánchez-Zapardiel
Elena Sánchez-Zapardiel
author_sort Ricardo Cuesta-Martín de la Cámara
collection DOAJ
description BackgroundEpstein-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.MethodsThirty-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.ResultsPolyfunctional 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).ConclusionPolyfunctional 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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spelling doaj-art-c8293f941f7f42a2bdd42cb4644129a32025-08-20T01:54:25ZengFrontiers Media S.A.Frontiers in Immunology1664-32242024-10-011510.3389/fimmu.2024.14794721479472Epstein-Barr virus-specific T-cell response in pediatric liver transplant recipients: a cross-sectional study by multiparametric flow cytometryRicardo Cuesta-Martín de la Cámara0Ricardo Cuesta-Martín de la Cámara1Ricardo Cuesta-Martín de la Cámara2Andrea Torices-Pajares3Laura Miguel-Berenguel4Keren Reche-Yebra5Esteban Frauca-Remacha6Esteban Frauca-Remacha7Esteban Frauca-Remacha8Loreto Hierro-Llanillo9Loreto Hierro-Llanillo10Loreto Hierro-Llanillo11Gema Muñoz-Bartolo12Gema Muñoz-Bartolo13Gema Muñoz-Bartolo14María Dolores Lledín-Barbacho15María Dolores Lledín-Barbacho16María Dolores Lledín-Barbacho17Almudena Gutiérrez-Arroyo18Ana Martínez-Feito19Eduardo López-Granados20Eduardo López-Granados21Eduardo López-Granados22Eduardo López-Granados23Elena Sánchez-Zapardiel24Elena Sánchez-Zapardiel25Elena Sánchez-Zapardiel26Clinical Immunology Department, University Hospital La Paz, Madrid, SpainLymphocyte Pathophysiology in Immunodeficiencies Group, La Paz Institute for Health Research (IdiPAZ), Madrid, SpainMedicine and surgery Department, Autonomous University of Madrid, Madrid, SpainLymphocyte Pathophysiology in Immunodeficiencies Group, La Paz Institute for Health Research (IdiPAZ), Madrid, SpainClinical Immunology Department, University Hospital La Paz, Madrid, SpainLymphocyte Pathophysiology in Immunodeficiencies Group, La Paz Institute for Health Research (IdiPAZ), Madrid, SpainPaediatric Hepatology Department, University Hospital La Paz, Madrid, SpainEuropean Reference Network (ERN) RARE LIVER, Madrid, SpainEuropean Reference Network (ERN) TransplantChild, Madrid, SpainPaediatric Hepatology Department, University Hospital La Paz, Madrid, SpainEuropean Reference Network (ERN) RARE LIVER, Madrid, SpainEuropean Reference Network (ERN) TransplantChild, Madrid, SpainPaediatric Hepatology Department, University Hospital La Paz, Madrid, SpainEuropean Reference Network (ERN) RARE LIVER, Madrid, SpainEuropean Reference Network (ERN) TransplantChild, Madrid, SpainPaediatric Hepatology Department, University Hospital La Paz, Madrid, SpainEuropean Reference Network (ERN) RARE LIVER, Madrid, SpainEuropean Reference Network (ERN) TransplantChild, Madrid, SpainMicrobiology Department, University Hospital La Paz, Madrid, SpainClinical Immunology Department, University Hospital La Paz, Madrid, SpainClinical Immunology Department, University Hospital La Paz, Madrid, SpainLymphocyte Pathophysiology in Immunodeficiencies Group, La Paz Institute for Health Research (IdiPAZ), Madrid, SpainEuropean Reference Network (ERN) TransplantChild, Madrid, SpainCentre for Biomedical Network Research on rare diseases (CIBERER U767), Madrid, SpainClinical Immunology Department, University Hospital La Paz, Madrid, SpainLymphocyte Pathophysiology in Immunodeficiencies Group, La Paz Institute for Health Research (IdiPAZ), Madrid, SpainEuropean Reference Network (ERN) TransplantChild, Madrid, SpainBackgroundEpstein-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.MethodsThirty-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.ResultsPolyfunctional 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).ConclusionPolyfunctional 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.https://www.frontiersin.org/articles/10.3389/fimmu.2024.1479472/fullliver transplantationEpstein-Barr virus infectionscellular immunityflow cytometrycytokinessurface antigens
spellingShingle Ricardo Cuesta-Martín de la Cámara
Ricardo Cuesta-Martín de la Cámara
Ricardo Cuesta-Martín de la Cámara
Andrea Torices-Pajares
Laura Miguel-Berenguel
Keren Reche-Yebra
Esteban Frauca-Remacha
Esteban Frauca-Remacha
Esteban Frauca-Remacha
Loreto Hierro-Llanillo
Loreto Hierro-Llanillo
Loreto Hierro-Llanillo
Gema Muñoz-Bartolo
Gema Muñoz-Bartolo
Gema Muñoz-Bartolo
María Dolores Lledín-Barbacho
María Dolores Lledín-Barbacho
María Dolores Lledín-Barbacho
Almudena Gutiérrez-Arroyo
Ana Martínez-Feito
Eduardo López-Granados
Eduardo López-Granados
Eduardo López-Granados
Eduardo López-Granados
Elena Sánchez-Zapardiel
Elena Sánchez-Zapardiel
Elena Sánchez-Zapardiel
Epstein-Barr virus-specific T-cell response in pediatric liver transplant recipients: a cross-sectional study by multiparametric flow cytometry
Frontiers in Immunology
liver transplantation
Epstein-Barr virus infections
cellular immunity
flow cytometry
cytokines
surface antigens
title Epstein-Barr virus-specific T-cell response in pediatric liver transplant recipients: a cross-sectional study by multiparametric flow cytometry
title_full Epstein-Barr virus-specific T-cell response in pediatric liver transplant recipients: a cross-sectional study by multiparametric flow cytometry
title_fullStr Epstein-Barr virus-specific T-cell response in pediatric liver transplant recipients: a cross-sectional study by multiparametric flow cytometry
title_full_unstemmed Epstein-Barr virus-specific T-cell response in pediatric liver transplant recipients: a cross-sectional study by multiparametric flow cytometry
title_short Epstein-Barr virus-specific T-cell response in pediatric liver transplant recipients: a cross-sectional study by multiparametric flow cytometry
title_sort epstein barr virus specific t cell response in pediatric liver transplant recipients a cross sectional study by multiparametric flow cytometry
topic liver transplantation
Epstein-Barr virus infections
cellular immunity
flow cytometry
cytokines
surface antigens
url https://www.frontiersin.org/articles/10.3389/fimmu.2024.1479472/full
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