Dysfunctional Epstein-Barr virus (EBV)-specific CD8(+) T lymphocytes and increased EBV load in HIV-1 infected individuals progressing to AIDS-related non-Hodgkin lymphoma.

Acquired immunodeficiency syndrome-related non-Hodgkin lymphomas (AIDS-NHL) are thought to arise because of loss of Epstein-Barr Virus (EBV)-specific cellular immunity. Here, an investigation was done to determine whether cellular immunity to EBV is lost because of physical loss or dysfunction of EB...

Full description

Bibliographic Details
Main Authors: van Baarle, D, Hovenkamp, E, Callan, M, Wolthers, K, Kostense, S, Tan, L, Niesters, H, Osterhaus, A, Mcmichael, A, van Oers, M, Miedema, F
Format: Journal article
Language:English
Published: 2001
_version_ 1826282275986210816
author van Baarle, D
Hovenkamp, E
Callan, M
Wolthers, K
Kostense, S
Tan, L
Niesters, H
Osterhaus, A
Mcmichael, A
van Oers, M
Miedema, F
author_facet van Baarle, D
Hovenkamp, E
Callan, M
Wolthers, K
Kostense, S
Tan, L
Niesters, H
Osterhaus, A
Mcmichael, A
van Oers, M
Miedema, F
author_sort van Baarle, D
collection OXFORD
description Acquired immunodeficiency syndrome-related non-Hodgkin lymphomas (AIDS-NHL) are thought to arise because of loss of Epstein-Barr Virus (EBV)-specific cellular immunity. Here, an investigation was done to determine whether cellular immunity to EBV is lost because of physical loss or dysfunction of EBV-specific cytotoxic T cells. Data on EBV-specific cellular immunity were correlated with EBV load. For comparison, individuals who progressed to AIDS with opportunistic infections (AIDS-OI) and long-term asymptomatics (LTAs) were studied. The number of virus-specific T cells was detected using tetrameric HLA-EBV-peptide complexes; function of these EBV-specific T cells was determined using the interferon-gamma (IFN-gamma) Elispot assay. It was observed that EBV-specific CD8(+) T cells were present in normal numbers in human immunodeficiency virus (HIV)-infected individuals. However, their functional capacity was decreased compared with HIV(-) individuals. In AIDS-NHL patients, EBV-specific T cells were not physically lost in the course of HIV-1 infection but showed progressive loss of their capability to produce IFN-gamma in response to EBV peptides. This loss of function correlated with lower CD4(+) T-cell numbers and was accompanied by increasing EBV load. In HIV-1-infected LTA individuals, in whom CD4(+) T-cell numbers were maintained, and progressors to AIDS-OI, IFN-gamma-producing EBV-specific T cells were stable and EBV load remained stable or decreased in the course of HIV infection, suggestive of immune control. Our data indicate that functional loss of EBV-specific CD8(+) T cells with a concomitant increase in EBV load may play a role in the pathogenesis of AIDS-NHL.
first_indexed 2024-03-07T00:41:23Z
format Journal article
id oxford-uuid:8328ed2a-5430-4a69-af12-2bc689e8cffe
institution University of Oxford
language English
last_indexed 2024-03-07T00:41:23Z
publishDate 2001
record_format dspace
spelling oxford-uuid:8328ed2a-5430-4a69-af12-2bc689e8cffe2022-03-26T21:42:17ZDysfunctional Epstein-Barr virus (EBV)-specific CD8(+) T lymphocytes and increased EBV load in HIV-1 infected individuals progressing to AIDS-related non-Hodgkin lymphoma.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:8328ed2a-5430-4a69-af12-2bc689e8cffeEnglishSymplectic Elements at Oxford2001van Baarle, DHovenkamp, ECallan, MWolthers, KKostense, STan, LNiesters, HOsterhaus, AMcmichael, Avan Oers, MMiedema, FAcquired immunodeficiency syndrome-related non-Hodgkin lymphomas (AIDS-NHL) are thought to arise because of loss of Epstein-Barr Virus (EBV)-specific cellular immunity. Here, an investigation was done to determine whether cellular immunity to EBV is lost because of physical loss or dysfunction of EBV-specific cytotoxic T cells. Data on EBV-specific cellular immunity were correlated with EBV load. For comparison, individuals who progressed to AIDS with opportunistic infections (AIDS-OI) and long-term asymptomatics (LTAs) were studied. The number of virus-specific T cells was detected using tetrameric HLA-EBV-peptide complexes; function of these EBV-specific T cells was determined using the interferon-gamma (IFN-gamma) Elispot assay. It was observed that EBV-specific CD8(+) T cells were present in normal numbers in human immunodeficiency virus (HIV)-infected individuals. However, their functional capacity was decreased compared with HIV(-) individuals. In AIDS-NHL patients, EBV-specific T cells were not physically lost in the course of HIV-1 infection but showed progressive loss of their capability to produce IFN-gamma in response to EBV peptides. This loss of function correlated with lower CD4(+) T-cell numbers and was accompanied by increasing EBV load. In HIV-1-infected LTA individuals, in whom CD4(+) T-cell numbers were maintained, and progressors to AIDS-OI, IFN-gamma-producing EBV-specific T cells were stable and EBV load remained stable or decreased in the course of HIV infection, suggestive of immune control. Our data indicate that functional loss of EBV-specific CD8(+) T cells with a concomitant increase in EBV load may play a role in the pathogenesis of AIDS-NHL.
spellingShingle van Baarle, D
Hovenkamp, E
Callan, M
Wolthers, K
Kostense, S
Tan, L
Niesters, H
Osterhaus, A
Mcmichael, A
van Oers, M
Miedema, F
Dysfunctional Epstein-Barr virus (EBV)-specific CD8(+) T lymphocytes and increased EBV load in HIV-1 infected individuals progressing to AIDS-related non-Hodgkin lymphoma.
title Dysfunctional Epstein-Barr virus (EBV)-specific CD8(+) T lymphocytes and increased EBV load in HIV-1 infected individuals progressing to AIDS-related non-Hodgkin lymphoma.
title_full Dysfunctional Epstein-Barr virus (EBV)-specific CD8(+) T lymphocytes and increased EBV load in HIV-1 infected individuals progressing to AIDS-related non-Hodgkin lymphoma.
title_fullStr Dysfunctional Epstein-Barr virus (EBV)-specific CD8(+) T lymphocytes and increased EBV load in HIV-1 infected individuals progressing to AIDS-related non-Hodgkin lymphoma.
title_full_unstemmed Dysfunctional Epstein-Barr virus (EBV)-specific CD8(+) T lymphocytes and increased EBV load in HIV-1 infected individuals progressing to AIDS-related non-Hodgkin lymphoma.
title_short Dysfunctional Epstein-Barr virus (EBV)-specific CD8(+) T lymphocytes and increased EBV load in HIV-1 infected individuals progressing to AIDS-related non-Hodgkin lymphoma.
title_sort dysfunctional epstein barr virus ebv specific cd8 t lymphocytes and increased ebv load in hiv 1 infected individuals progressing to aids related non hodgkin lymphoma
work_keys_str_mv AT vanbaarled dysfunctionalepsteinbarrvirusebvspecificcd8tlymphocytesandincreasedebvloadinhiv1infectedindividualsprogressingtoaidsrelatednonhodgkinlymphoma
AT hovenkampe dysfunctionalepsteinbarrvirusebvspecificcd8tlymphocytesandincreasedebvloadinhiv1infectedindividualsprogressingtoaidsrelatednonhodgkinlymphoma
AT callanm dysfunctionalepsteinbarrvirusebvspecificcd8tlymphocytesandincreasedebvloadinhiv1infectedindividualsprogressingtoaidsrelatednonhodgkinlymphoma
AT wolthersk dysfunctionalepsteinbarrvirusebvspecificcd8tlymphocytesandincreasedebvloadinhiv1infectedindividualsprogressingtoaidsrelatednonhodgkinlymphoma
AT kostenses dysfunctionalepsteinbarrvirusebvspecificcd8tlymphocytesandincreasedebvloadinhiv1infectedindividualsprogressingtoaidsrelatednonhodgkinlymphoma
AT tanl dysfunctionalepsteinbarrvirusebvspecificcd8tlymphocytesandincreasedebvloadinhiv1infectedindividualsprogressingtoaidsrelatednonhodgkinlymphoma
AT niestersh dysfunctionalepsteinbarrvirusebvspecificcd8tlymphocytesandincreasedebvloadinhiv1infectedindividualsprogressingtoaidsrelatednonhodgkinlymphoma
AT osterhausa dysfunctionalepsteinbarrvirusebvspecificcd8tlymphocytesandincreasedebvloadinhiv1infectedindividualsprogressingtoaidsrelatednonhodgkinlymphoma
AT mcmichaela dysfunctionalepsteinbarrvirusebvspecificcd8tlymphocytesandincreasedebvloadinhiv1infectedindividualsprogressingtoaidsrelatednonhodgkinlymphoma
AT vanoersm dysfunctionalepsteinbarrvirusebvspecificcd8tlymphocytesandincreasedebvloadinhiv1infectedindividualsprogressingtoaidsrelatednonhodgkinlymphoma
AT miedemaf dysfunctionalepsteinbarrvirusebvspecificcd8tlymphocytesandincreasedebvloadinhiv1infectedindividualsprogressingtoaidsrelatednonhodgkinlymphoma