Functional heterogeneity and high frequencies of cytomegalovirus-specific CD8(+) T lymphocytes in healthy seropositive donors

Human cytomegalovirus (HCMV) infection is largely asymptomatic in the immunocompetent host, but remains a major cause of morbidity in immunosuppressed individuals. Using the recently described technique of staining antigen-specific CD8+ T cells with peptide-HLA tetrameric complexes, we have demonstr...

Full description

Bibliographic Details
Main Authors: Gillespie, G, Wills, MR, Appay, V, O'Callaghan, C, Murphy, M, Smith, N, Sissons, P, Rowland-Jones, S, Bell, J, Moss, P
Format: Journal article
Language:English
Published: 2000
_version_ 1797092577335312384
author Gillespie, G
Wills, MR
Appay, V
O'Callaghan, C
Murphy, M
Smith, N
Sissons, P
Rowland-Jones, S
Bell, J
Moss, P
author_facet Gillespie, G
Wills, MR
Appay, V
O'Callaghan, C
Murphy, M
Smith, N
Sissons, P
Rowland-Jones, S
Bell, J
Moss, P
author_sort Gillespie, G
collection OXFORD
description Human cytomegalovirus (HCMV) infection is largely asymptomatic in the immunocompetent host, but remains a major cause of morbidity in immunosuppressed individuals. Using the recently described technique of staining antigen-specific CD8+ T cells with peptide-HLA tetrameric complexes, we have demonstrated high levels of antigen-specific cells specific for HCMV peptides and show that this may exceed 4% of CD8+ T cells in immunocompetent donors. Moreover, by staining with tetramers in combination with antibodies to cell surface markers and intracellular cytokines, we demonstrate functional heterogeneity of HCMV-specific populations. A substantial proportion of these are effector cytotoxic T lymphocytes, as demonstrated by their ability to lyse peptide-pulsed targets in 'fresh' killing assays. These data suggest that the immune response to HCMV is periodically boosted by a low level of HCMV replication and that sustained immunological surveillance contributes to the maintenance of host-pathogen homeostasis. These observations should improve our understanding of the immunobiology of persistent viral infection.
first_indexed 2024-03-07T03:47:57Z
format Journal article
id oxford-uuid:c02c6132-a4ca-4511-9a8f-2649a7acb6f7
institution University of Oxford
language English
last_indexed 2024-03-07T03:47:57Z
publishDate 2000
record_format dspace
spelling oxford-uuid:c02c6132-a4ca-4511-9a8f-2649a7acb6f72022-03-27T05:52:40ZFunctional heterogeneity and high frequencies of cytomegalovirus-specific CD8(+) T lymphocytes in healthy seropositive donorsJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:c02c6132-a4ca-4511-9a8f-2649a7acb6f7EnglishSymplectic Elements at Oxford2000Gillespie, GWills, MRAppay, VO'Callaghan, CMurphy, MSmith, NSissons, PRowland-Jones, SBell, JMoss, PHuman cytomegalovirus (HCMV) infection is largely asymptomatic in the immunocompetent host, but remains a major cause of morbidity in immunosuppressed individuals. Using the recently described technique of staining antigen-specific CD8+ T cells with peptide-HLA tetrameric complexes, we have demonstrated high levels of antigen-specific cells specific for HCMV peptides and show that this may exceed 4% of CD8+ T cells in immunocompetent donors. Moreover, by staining with tetramers in combination with antibodies to cell surface markers and intracellular cytokines, we demonstrate functional heterogeneity of HCMV-specific populations. A substantial proportion of these are effector cytotoxic T lymphocytes, as demonstrated by their ability to lyse peptide-pulsed targets in 'fresh' killing assays. These data suggest that the immune response to HCMV is periodically boosted by a low level of HCMV replication and that sustained immunological surveillance contributes to the maintenance of host-pathogen homeostasis. These observations should improve our understanding of the immunobiology of persistent viral infection.
spellingShingle Gillespie, G
Wills, MR
Appay, V
O'Callaghan, C
Murphy, M
Smith, N
Sissons, P
Rowland-Jones, S
Bell, J
Moss, P
Functional heterogeneity and high frequencies of cytomegalovirus-specific CD8(+) T lymphocytes in healthy seropositive donors
title Functional heterogeneity and high frequencies of cytomegalovirus-specific CD8(+) T lymphocytes in healthy seropositive donors
title_full Functional heterogeneity and high frequencies of cytomegalovirus-specific CD8(+) T lymphocytes in healthy seropositive donors
title_fullStr Functional heterogeneity and high frequencies of cytomegalovirus-specific CD8(+) T lymphocytes in healthy seropositive donors
title_full_unstemmed Functional heterogeneity and high frequencies of cytomegalovirus-specific CD8(+) T lymphocytes in healthy seropositive donors
title_short Functional heterogeneity and high frequencies of cytomegalovirus-specific CD8(+) T lymphocytes in healthy seropositive donors
title_sort functional heterogeneity and high frequencies of cytomegalovirus specific cd8 t lymphocytes in healthy seropositive donors
work_keys_str_mv AT gillespieg functionalheterogeneityandhighfrequenciesofcytomegalovirusspecificcd8tlymphocytesinhealthyseropositivedonors
AT willsmr functionalheterogeneityandhighfrequenciesofcytomegalovirusspecificcd8tlymphocytesinhealthyseropositivedonors
AT appayv functionalheterogeneityandhighfrequenciesofcytomegalovirusspecificcd8tlymphocytesinhealthyseropositivedonors
AT ocallaghanc functionalheterogeneityandhighfrequenciesofcytomegalovirusspecificcd8tlymphocytesinhealthyseropositivedonors
AT murphym functionalheterogeneityandhighfrequenciesofcytomegalovirusspecificcd8tlymphocytesinhealthyseropositivedonors
AT smithn functionalheterogeneityandhighfrequenciesofcytomegalovirusspecificcd8tlymphocytesinhealthyseropositivedonors
AT sissonsp functionalheterogeneityandhighfrequenciesofcytomegalovirusspecificcd8tlymphocytesinhealthyseropositivedonors
AT rowlandjoness functionalheterogeneityandhighfrequenciesofcytomegalovirusspecificcd8tlymphocytesinhealthyseropositivedonors
AT bellj functionalheterogeneityandhighfrequenciesofcytomegalovirusspecificcd8tlymphocytesinhealthyseropositivedonors
AT mossp functionalheterogeneityandhighfrequenciesofcytomegalovirusspecificcd8tlymphocytesinhealthyseropositivedonors