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Article: Co-infection of Cytomegalovirus and Epstein-Barr Virus Diminishes the Frequency of CD56dimNKG2A+KIR- NK Cells and Contributes to Suboptimal Control of EBV in Immunosuppressed Children With Post-transplant Lymphoproliferative Disorder

TitleCo-infection of Cytomegalovirus and Epstein-Barr Virus Diminishes the Frequency of CD56dimNKG2A+KIR- NK Cells and Contributes to Suboptimal Control of EBV in Immunosuppressed Children With Post-transplant Lymphoproliferative Disorder
Authors
KeywordsEBV
post-transplant lymphoproliferative disorder
infectious mononucleosis
natural killer cells
NKG2A
Issue Date2020
PublisherFrontiers Research Foundation. The Journal's web site is located at http://www.frontiersin.org/immunology
Citation
Frontiers in Immunology, 2020, v. 11, p. article no. 1231 How to Cite?
AbstractPost-transplant lymphoproliferative disorder (PTLD) is a rare but potentially life-threatening complication, frequently associated with Epstein-Barr virus (EBV), which develops after solid organ or stem cell transplantation. Immunosuppression received by transplant recipients has a significant impact on the development of PTLD by suppressing the function of T cells. The preferential proliferation of NKG2A-positive natural killer (NK) cells during primary symptomatic EBV infection known as infectious mononucleosis (IM) and their reactivity toward EBV-infected B cells point to a role of NK cell in the immune control of EBV. However, NK cell-mediated immune response to EBV in immunosuppressed transplant recipients who develop PTLD remains unclear. In this study, we longitudinally analyzed the phenotype and function of different NK cell subsets in a cohort of pediatric liver transplant patients who develop PTLD and compared them to those of children with IM. We found persistently elevated plasma EBV DNA levels in the PTLD patients indicating suboptimal anti-viral immune control. PTLD patients had markedly decreased frequency of CD56dimNKG2A+Killer Immunoglobulin-like receptor (KIR)− NK cells from the time of diagnosis through remission compared to those of IM patients. Whilst the proliferation of CD56dimNKG2A+KIR− NK cells was diminished in PTLD patients, this NK cell subset maintained its ability to potently degranulate against EBV-infected B cells. Compared to cytomegalovirus (CMV)-seropositive and -negative IM patients, PTLD patients co-infected with CMV and EBV had significantly higher levels of a CMV-associated CD56dimNKG2ChiCD57+NKG2A−KIR+ NK cell subset accumulating at the expense of NKG2A+KIR− NK cells. Taken together, our data indicate that co-infection of CMV and EBV diminishes the frequency of CD56dimNKG2A+KIR− NK cells and contributes to suboptimal control of EBV in immunosuppressed children with PTLD. © Copyright © 2020 Lam, Azzi, Hui, Wong, McHugh, Caduff, Chan, Münz and Chiang.
Persistent Identifierhttp://hdl.handle.net/10722/289796
ISSN
2023 Impact Factor: 5.7
2023 SCImago Journal Rankings: 1.868
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorLAM, JKP-
dc.contributor.authorAzzi, T-
dc.contributor.authorHui, KF-
dc.contributor.authorWong, AMG-
dc.contributor.authorMcHugh, D-
dc.contributor.authorCaduff, N-
dc.contributor.authorChan, KH-
dc.contributor.authorMünz, C-
dc.contributor.authorChiang, AKS-
dc.date.accessioned2020-10-22T08:17:36Z-
dc.date.available2020-10-22T08:17:36Z-
dc.date.issued2020-
dc.identifier.citationFrontiers in Immunology, 2020, v. 11, p. article no. 1231-
dc.identifier.issn1664-3224-
dc.identifier.urihttp://hdl.handle.net/10722/289796-
dc.description.abstractPost-transplant lymphoproliferative disorder (PTLD) is a rare but potentially life-threatening complication, frequently associated with Epstein-Barr virus (EBV), which develops after solid organ or stem cell transplantation. Immunosuppression received by transplant recipients has a significant impact on the development of PTLD by suppressing the function of T cells. The preferential proliferation of NKG2A-positive natural killer (NK) cells during primary symptomatic EBV infection known as infectious mononucleosis (IM) and their reactivity toward EBV-infected B cells point to a role of NK cell in the immune control of EBV. However, NK cell-mediated immune response to EBV in immunosuppressed transplant recipients who develop PTLD remains unclear. In this study, we longitudinally analyzed the phenotype and function of different NK cell subsets in a cohort of pediatric liver transplant patients who develop PTLD and compared them to those of children with IM. We found persistently elevated plasma EBV DNA levels in the PTLD patients indicating suboptimal anti-viral immune control. PTLD patients had markedly decreased frequency of CD56dimNKG2A+Killer Immunoglobulin-like receptor (KIR)− NK cells from the time of diagnosis through remission compared to those of IM patients. Whilst the proliferation of CD56dimNKG2A+KIR− NK cells was diminished in PTLD patients, this NK cell subset maintained its ability to potently degranulate against EBV-infected B cells. Compared to cytomegalovirus (CMV)-seropositive and -negative IM patients, PTLD patients co-infected with CMV and EBV had significantly higher levels of a CMV-associated CD56dimNKG2ChiCD57+NKG2A−KIR+ NK cell subset accumulating at the expense of NKG2A+KIR− NK cells. Taken together, our data indicate that co-infection of CMV and EBV diminishes the frequency of CD56dimNKG2A+KIR− NK cells and contributes to suboptimal control of EBV in immunosuppressed children with PTLD. © Copyright © 2020 Lam, Azzi, Hui, Wong, McHugh, Caduff, Chan, Münz and Chiang.-
dc.languageeng-
dc.publisherFrontiers Research Foundation. The Journal's web site is located at http://www.frontiersin.org/immunology-
dc.relation.ispartofFrontiers in Immunology-
dc.rightsThis Document is Protected by copyright and was first published by Frontiers. All rights reserved. It is reproduced with permission.-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjectEBV-
dc.subjectpost-transplant lymphoproliferative disorder-
dc.subjectinfectious mononucleosis-
dc.subjectnatural killer cells-
dc.subjectNKG2A-
dc.titleCo-infection of Cytomegalovirus and Epstein-Barr Virus Diminishes the Frequency of CD56dimNKG2A+KIR- NK Cells and Contributes to Suboptimal Control of EBV in Immunosuppressed Children With Post-transplant Lymphoproliferative Disorder-
dc.typeArticle-
dc.identifier.emailChan, KH: chankh2@hkucc.hku.hk-
dc.identifier.emailChiang, AKS: chiangak@hku.hk-
dc.identifier.authorityChan, KH=rp01921-
dc.identifier.authorityChiang, AKS=rp00403-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.3389/fimmu.2020.01231-
dc.identifier.pmid32625211-
dc.identifier.pmcidPMC7311655-
dc.identifier.scopuseid_2-s2.0-85087143253-
dc.identifier.hkuros317463-
dc.identifier.volume11-
dc.identifier.spagearticle no. 1231-
dc.identifier.epagearticle no. 1231-
dc.identifier.isiWOS:000546877400001-
dc.publisher.placeSwitzerland-
dc.identifier.issnl1664-3224-

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