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...
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Format: | Journal article |
Language: | English |
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2000
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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 |
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