Human immunodeficiency virus type 1- and cytomegalovirus-specific cytotoxic T lymphocytes can persist at high frequency for prolonged periods in the absence of circulating peripheral CD4(+) T cells.

CD4(+) T cells are thought to be critical in the maintenance of virus-specific CD8(+) cytotoxic T-cell (CTL) responses. In human immunodeficiency virus type 1 (HIV-1) infection, a selective decline in HIV-1-specific CTL as the CD4(+) T-cell count decreases has been reported. Using HLA-peptide tetram...

Full description

Bibliographic Details
Main Authors: Spiegel, H, Ogg, G, DeFalcon, E, Sheehy, M, Monard, S, Haslett, P, Gillespie, G, Donahoe, S, Pollack, H, Borkowsky, W, Mcmichael, A, Nixon, D
Format: Journal article
Language:English
Published: 2000
_version_ 1797099615560925184
author Spiegel, H
Ogg, G
DeFalcon, E
Sheehy, M
Monard, S
Haslett, P
Gillespie, G
Donahoe, S
Pollack, H
Borkowsky, W
Mcmichael, A
Nixon, D
author_facet Spiegel, H
Ogg, G
DeFalcon, E
Sheehy, M
Monard, S
Haslett, P
Gillespie, G
Donahoe, S
Pollack, H
Borkowsky, W
Mcmichael, A
Nixon, D
author_sort Spiegel, H
collection OXFORD
description CD4(+) T cells are thought to be critical in the maintenance of virus-specific CD8(+) cytotoxic T-cell (CTL) responses. In human immunodeficiency virus type 1 (HIV-1) infection, a selective decline in HIV-1-specific CTL as the CD4(+) T-cell count decreases has been reported. Using HLA-peptide tetrameric complexes, we show the presence at high frequency of HIV-1- and cytomegalovirus-specific CD8(+) T cells when the peripheral CD4(+) T-cell count was low or zero in three HIV-1-infected patients. No direct virus-specific CD8(+)-mediated effector activity was seen in these subjects, suggesting antigen unresponsiveness, although tetramer-sorted cells could be expanded in vitro in the presence of interleukin-2 into responsive effector cells. Thus, virus-specific CD8(+) T cells can be maintained in the peripheral circulation at high frequency in the absence of circulating peripheral CD4(+) T cells, but these cells may lack direct effector activity. Strategies designed to overcome this antigen unresponsiveness may be of value in therapies for the treatment of AIDS.
first_indexed 2024-03-07T05:26:12Z
format Journal article
id oxford-uuid:e0a4a7c1-f555-4b19-a530-206e3fb748fe
institution University of Oxford
language English
last_indexed 2024-03-07T05:26:12Z
publishDate 2000
record_format dspace
spelling oxford-uuid:e0a4a7c1-f555-4b19-a530-206e3fb748fe2022-03-27T09:48:45ZHuman immunodeficiency virus type 1- and cytomegalovirus-specific cytotoxic T lymphocytes can persist at high frequency for prolonged periods in the absence of circulating peripheral CD4(+) T cells.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:e0a4a7c1-f555-4b19-a530-206e3fb748feEnglishSymplectic Elements at Oxford2000Spiegel, HOgg, GDeFalcon, ESheehy, MMonard, SHaslett, PGillespie, GDonahoe, SPollack, HBorkowsky, WMcmichael, ANixon, DCD4(+) T cells are thought to be critical in the maintenance of virus-specific CD8(+) cytotoxic T-cell (CTL) responses. In human immunodeficiency virus type 1 (HIV-1) infection, a selective decline in HIV-1-specific CTL as the CD4(+) T-cell count decreases has been reported. Using HLA-peptide tetrameric complexes, we show the presence at high frequency of HIV-1- and cytomegalovirus-specific CD8(+) T cells when the peripheral CD4(+) T-cell count was low or zero in three HIV-1-infected patients. No direct virus-specific CD8(+)-mediated effector activity was seen in these subjects, suggesting antigen unresponsiveness, although tetramer-sorted cells could be expanded in vitro in the presence of interleukin-2 into responsive effector cells. Thus, virus-specific CD8(+) T cells can be maintained in the peripheral circulation at high frequency in the absence of circulating peripheral CD4(+) T cells, but these cells may lack direct effector activity. Strategies designed to overcome this antigen unresponsiveness may be of value in therapies for the treatment of AIDS.
spellingShingle Spiegel, H
Ogg, G
DeFalcon, E
Sheehy, M
Monard, S
Haslett, P
Gillespie, G
Donahoe, S
Pollack, H
Borkowsky, W
Mcmichael, A
Nixon, D
Human immunodeficiency virus type 1- and cytomegalovirus-specific cytotoxic T lymphocytes can persist at high frequency for prolonged periods in the absence of circulating peripheral CD4(+) T cells.
title Human immunodeficiency virus type 1- and cytomegalovirus-specific cytotoxic T lymphocytes can persist at high frequency for prolonged periods in the absence of circulating peripheral CD4(+) T cells.
title_full Human immunodeficiency virus type 1- and cytomegalovirus-specific cytotoxic T lymphocytes can persist at high frequency for prolonged periods in the absence of circulating peripheral CD4(+) T cells.
title_fullStr Human immunodeficiency virus type 1- and cytomegalovirus-specific cytotoxic T lymphocytes can persist at high frequency for prolonged periods in the absence of circulating peripheral CD4(+) T cells.
title_full_unstemmed Human immunodeficiency virus type 1- and cytomegalovirus-specific cytotoxic T lymphocytes can persist at high frequency for prolonged periods in the absence of circulating peripheral CD4(+) T cells.
title_short Human immunodeficiency virus type 1- and cytomegalovirus-specific cytotoxic T lymphocytes can persist at high frequency for prolonged periods in the absence of circulating peripheral CD4(+) T cells.
title_sort human immunodeficiency virus type 1 and cytomegalovirus specific cytotoxic t lymphocytes can persist at high frequency for prolonged periods in the absence of circulating peripheral cd4 t cells
work_keys_str_mv AT spiegelh humanimmunodeficiencyvirustype1andcytomegalovirusspecificcytotoxictlymphocytescanpersistathighfrequencyforprolongedperiodsintheabsenceofcirculatingperipheralcd4tcells
AT oggg humanimmunodeficiencyvirustype1andcytomegalovirusspecificcytotoxictlymphocytescanpersistathighfrequencyforprolongedperiodsintheabsenceofcirculatingperipheralcd4tcells
AT defalcone humanimmunodeficiencyvirustype1andcytomegalovirusspecificcytotoxictlymphocytescanpersistathighfrequencyforprolongedperiodsintheabsenceofcirculatingperipheralcd4tcells
AT sheehym humanimmunodeficiencyvirustype1andcytomegalovirusspecificcytotoxictlymphocytescanpersistathighfrequencyforprolongedperiodsintheabsenceofcirculatingperipheralcd4tcells
AT monards humanimmunodeficiencyvirustype1andcytomegalovirusspecificcytotoxictlymphocytescanpersistathighfrequencyforprolongedperiodsintheabsenceofcirculatingperipheralcd4tcells
AT haslettp humanimmunodeficiencyvirustype1andcytomegalovirusspecificcytotoxictlymphocytescanpersistathighfrequencyforprolongedperiodsintheabsenceofcirculatingperipheralcd4tcells
AT gillespieg humanimmunodeficiencyvirustype1andcytomegalovirusspecificcytotoxictlymphocytescanpersistathighfrequencyforprolongedperiodsintheabsenceofcirculatingperipheralcd4tcells
AT donahoes humanimmunodeficiencyvirustype1andcytomegalovirusspecificcytotoxictlymphocytescanpersistathighfrequencyforprolongedperiodsintheabsenceofcirculatingperipheralcd4tcells
AT pollackh humanimmunodeficiencyvirustype1andcytomegalovirusspecificcytotoxictlymphocytescanpersistathighfrequencyforprolongedperiodsintheabsenceofcirculatingperipheralcd4tcells
AT borkowskyw humanimmunodeficiencyvirustype1andcytomegalovirusspecificcytotoxictlymphocytescanpersistathighfrequencyforprolongedperiodsintheabsenceofcirculatingperipheralcd4tcells
AT mcmichaela humanimmunodeficiencyvirustype1andcytomegalovirusspecificcytotoxictlymphocytescanpersistathighfrequencyforprolongedperiodsintheabsenceofcirculatingperipheralcd4tcells
AT nixond humanimmunodeficiencyvirustype1andcytomegalovirusspecificcytotoxictlymphocytescanpersistathighfrequencyforprolongedperiodsintheabsenceofcirculatingperipheralcd4tcells