Cytomegalovirus-Specific T Cells in Pediatric Liver Transplant Recipients

Cytomegalovirus (CMV) infection is a major opportunistic infection after liver transplantation (LT) that necessitates monitoring. Because of the lack of studies in children, we aimed to investigate CMV-specific T cell immune reconstitution among pediatric LT recipients. The recipients were monitored...

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Main Authors: Songpon Getsuwan, Nopporn Apiwattanakul, Chatmanee Lertudomphonwanit, Suradej Hongeng, Sophida Boonsathorn, Wiparat Manuyakorn, Pornthep Tanpowpong, Usanarat Anurathapan, Kanchana Tangnararatchakit, Suporn Treepongkaruna
Format: Article
Language:English
Published: MDPI AG 2023-11-01
Series:Viruses
Subjects:
Online Access:https://www.mdpi.com/1999-4915/15/11/2213
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author Songpon Getsuwan
Nopporn Apiwattanakul
Chatmanee Lertudomphonwanit
Suradej Hongeng
Sophida Boonsathorn
Wiparat Manuyakorn
Pornthep Tanpowpong
Usanarat Anurathapan
Kanchana Tangnararatchakit
Suporn Treepongkaruna
author_facet Songpon Getsuwan
Nopporn Apiwattanakul
Chatmanee Lertudomphonwanit
Suradej Hongeng
Sophida Boonsathorn
Wiparat Manuyakorn
Pornthep Tanpowpong
Usanarat Anurathapan
Kanchana Tangnararatchakit
Suporn Treepongkaruna
author_sort Songpon Getsuwan
collection DOAJ
description Cytomegalovirus (CMV) infection is a major opportunistic infection after liver transplantation (LT) that necessitates monitoring. Because of the lack of studies in children, we aimed to investigate CMV-specific T cell immune reconstitution among pediatric LT recipients. The recipients were monitored for CMV infection and CMV-specific T cells from the start of immunosuppressive therapy until 48 weeks after LT. Clinically significant CMV viremia (csCMV) requiring preemptive therapy was defined as a CMV load of >2000 IU/mL. Peripheral blood CMV-specific T cells were analyzed by flow cytometry based on IFNγ secretion upon stimulation with CMV antigens including immediate early protein 1 (IE1) Ag, phosphoprotein 65 (pp65) Ag, and whole CMV lysate (wCMV). Of the 41 patients who underwent LT, 20 (48.8%) had csCMV. Most (17/20 patients) were asymptomatic and characterized as experiencing CMV reactivation. The onset of csCMV occurred approximately 7 weeks after LT (interquartile range: 4–12.9); csCMV rarely recurred after preemptive therapy. Lower pp65-specific CD8+ T cell response was associated with the occurrence of csCMV (<i>p</i> = 0.01) and correlated with increased viral load at the time of csCMV diagnosis (ρ = −0.553, <i>p</i> = 0.02). Moreover, those with csCMV had lower percentages of IE1-specific CD4+ and wCMV-reactive CD4+ T cells at 12 weeks after LT (<i>p</i> = 0.03 and <i>p</i> = 0.01, respectively). Despite intense immunosuppressive therapy, CMV-specific T cell immune reconstitution occurred in pediatric patients post-LT, which could confer protection against CMV reactivation.
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spelling doaj.art-e6c29e94ef624dfca6d6fec2f4c575192023-11-24T15:10:48ZengMDPI AGViruses1999-49152023-11-011511221310.3390/v15112213Cytomegalovirus-Specific T Cells in Pediatric Liver Transplant RecipientsSongpon Getsuwan0Nopporn Apiwattanakul1Chatmanee Lertudomphonwanit2Suradej Hongeng3Sophida Boonsathorn4Wiparat Manuyakorn5Pornthep Tanpowpong6Usanarat Anurathapan7Kanchana Tangnararatchakit8Suporn Treepongkaruna9Division of Gastroenterology, Department of Pediatrics, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok 10400, ThailandDivision of Infectious Disease, Department of Pediatrics, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok 10400, ThailandDivision of Gastroenterology, Department of Pediatrics, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok 10400, ThailandDivision of Hematology and Oncology, Department of Pediatrics, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok 10400, ThailandDivision of Infectious Disease, Department of Pediatrics, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok 10400, ThailandDivision of Allergy, Department of Pediatrics, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok 10400, ThailandDivision of Gastroenterology, Department of Pediatrics, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok 10400, ThailandDivision of Hematology and Oncology, Department of Pediatrics, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok 10400, ThailandDivision of Nephrology, Department of Pediatrics, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok 10400, ThailandDivision of Gastroenterology, Department of Pediatrics, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok 10400, ThailandCytomegalovirus (CMV) infection is a major opportunistic infection after liver transplantation (LT) that necessitates monitoring. Because of the lack of studies in children, we aimed to investigate CMV-specific T cell immune reconstitution among pediatric LT recipients. The recipients were monitored for CMV infection and CMV-specific T cells from the start of immunosuppressive therapy until 48 weeks after LT. Clinically significant CMV viremia (csCMV) requiring preemptive therapy was defined as a CMV load of >2000 IU/mL. Peripheral blood CMV-specific T cells were analyzed by flow cytometry based on IFNγ secretion upon stimulation with CMV antigens including immediate early protein 1 (IE1) Ag, phosphoprotein 65 (pp65) Ag, and whole CMV lysate (wCMV). Of the 41 patients who underwent LT, 20 (48.8%) had csCMV. Most (17/20 patients) were asymptomatic and characterized as experiencing CMV reactivation. The onset of csCMV occurred approximately 7 weeks after LT (interquartile range: 4–12.9); csCMV rarely recurred after preemptive therapy. Lower pp65-specific CD8+ T cell response was associated with the occurrence of csCMV (<i>p</i> = 0.01) and correlated with increased viral load at the time of csCMV diagnosis (ρ = −0.553, <i>p</i> = 0.02). Moreover, those with csCMV had lower percentages of IE1-specific CD4+ and wCMV-reactive CD4+ T cells at 12 weeks after LT (<i>p</i> = 0.03 and <i>p</i> = 0.01, respectively). Despite intense immunosuppressive therapy, CMV-specific T cell immune reconstitution occurred in pediatric patients post-LT, which could confer protection against CMV reactivation.https://www.mdpi.com/1999-4915/15/11/2213cytomegalovirusliver transplantationchildrenimmunologyT cells
spellingShingle Songpon Getsuwan
Nopporn Apiwattanakul
Chatmanee Lertudomphonwanit
Suradej Hongeng
Sophida Boonsathorn
Wiparat Manuyakorn
Pornthep Tanpowpong
Usanarat Anurathapan
Kanchana Tangnararatchakit
Suporn Treepongkaruna
Cytomegalovirus-Specific T Cells in Pediatric Liver Transplant Recipients
Viruses
cytomegalovirus
liver transplantation
children
immunology
T cells
title Cytomegalovirus-Specific T Cells in Pediatric Liver Transplant Recipients
title_full Cytomegalovirus-Specific T Cells in Pediatric Liver Transplant Recipients
title_fullStr Cytomegalovirus-Specific T Cells in Pediatric Liver Transplant Recipients
title_full_unstemmed Cytomegalovirus-Specific T Cells in Pediatric Liver Transplant Recipients
title_short Cytomegalovirus-Specific T Cells in Pediatric Liver Transplant Recipients
title_sort cytomegalovirus specific t cells in pediatric liver transplant recipients
topic cytomegalovirus
liver transplantation
children
immunology
T cells
url https://www.mdpi.com/1999-4915/15/11/2213
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