T Cell Homeostasis Disturbances in a Cohort of Long-Term Elite Controllers of HIV Infection.

Elite controllers (ECs) are people living with HIV (PLWH) able to control HIV replication without antiretroviral therapy and have been proposed as a model of a functional HIV cure. Much evidence suggests that this spontaneous control of HIV has a cost in terms of T cell homeostasis alterations. We p...

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Autores: Benito, José Miguel, Jiménez-Carretero, Daniel, Restrepo, Clara, Ligos, José M, Valentín-Quiroga, Jaime, Mahillo, Ignacio, Cabello, Alfonso, López-Collazo, Eduardo, Sánchez-Cabo, Fátima, Górgolas, Miguel, Estrada, Vicente, Rallón, Norma
Tipo de recurso: artículo
Fecha de publicación:2024
País:España
Institución:Instituto de Salud Carlos III (ISCIII)
Repositorio:Repisalud
Idioma:inglés
OAI Identifier:oai:repisalud.isciii.es:20.500.12105/20210
Acceso en línea:http://hdl.handle.net/20.500.12105/20210
Access Level:acceso abierto
Palabra clave:HIV Infections
Homeostasis
CD4-Positive T-Lymphocytes
CD8-Positive T-Lymphocytes
Humans
Male
Female
Adult
Middle Aged
HIV Long-Term Survivors
HIV-1
Cohort Studies
Viral Load
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spelling T Cell Homeostasis Disturbances in a Cohort of Long-Term Elite Controllers of HIV Infection.Benito, José MiguelJiménez-Carretero, DanielRestrepo, ClaraLigos, José MValentín-Quiroga, JaimeMahillo, IgnacioCabello, AlfonsoLópez-Collazo, EduardoSánchez-Cabo, FátimaGórgolas, MiguelEstrada, VicenteRallón, NormaHIV InfectionsHomeostasisCD4-Positive T-LymphocytesCD8-Positive T-LymphocytesHumansMaleFemaleAdultMiddle AgedHIV Long-Term SurvivorsHIV-1Cohort StudiesViral LoadElite controllers (ECs) are people living with HIV (PLWH) able to control HIV replication without antiretroviral therapy and have been proposed as a model of a functional HIV cure. Much evidence suggests that this spontaneous control of HIV has a cost in terms of T cell homeostasis alterations. We performed a deep phenotypic study to obtain insight into T cell homeostasis disturbances in ECs maintaining long-term virologic and immunologic control of HIV (long-term elite controllers; LTECs). Forty-seven PLWH were included: 22 LTECs, 15 non-controllers under successful antiretroviral therapy (onART), and 10 non-controllers not receiving ART (offART). Twenty uninfected participants (UCs) were included as a reference. T cell homeostasis was analyzed by spectral flow cytometry and data were analyzed using dimensionality reduction and clustering using R software v3.3.2. Dimensionality reduction and clustering yielded 57 and 54 different CD4 and CD8 T cell clusters, respectively. The offART group showed the highest perturbation of T cell homeostasis, with 18 CD4 clusters and 15 CD8 clusters significantly different from those of UCs. Most of these alterations were reverted in the onART group. Interestingly, LTECs presented several disturbances of T cell homeostasis with 15 CD4 clusters and 13 CD8 clusters different from UC. Moreover, there was a specific profile of T cell homeostasis alterations associated with LTECs, characterized by increases in clusters of naïve T cells, increases in clusters of non-senescent effector CD8 cells, and increases in clusters of central memory CD4 cells. These results demonstrate that, compared to ART-mediated control of HIV, the spontaneous control of HIV is associated with several disturbances in CD4 and CD8 T cell homeostasis. These alterations could be related to the existence of a potent and efficient virus-specific T cell response, and to the ability to halt disease progression by maintaining an adequate pool of CD4 T cells.Multidisciplinary Digital Publishing Institute (MDPI)Instituto de Salud Carlos IIIUnión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF)20242024-07-0820242024-05-2920242024-05-29journal articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/20.500.12105/20210reponame:Repisaludinstname:Instituto de Salud Carlos III (ISCIII)Inglésengopen accesshttp://purl.org/coar/access_right/c_abf2Atribución 4.0 Internacionalhttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:repisalud.isciii.es:20.500.12105/202102026-06-12T12:43:37Z
dc.title.none.fl_str_mv T Cell Homeostasis Disturbances in a Cohort of Long-Term Elite Controllers of HIV Infection.
title T Cell Homeostasis Disturbances in a Cohort of Long-Term Elite Controllers of HIV Infection.
spellingShingle T Cell Homeostasis Disturbances in a Cohort of Long-Term Elite Controllers of HIV Infection.
Benito, José Miguel
HIV Infections
Homeostasis
CD4-Positive T-Lymphocytes
CD8-Positive T-Lymphocytes
Humans
Male
Female
Adult
Middle Aged
HIV Long-Term Survivors
HIV-1
Cohort Studies
Viral Load
title_short T Cell Homeostasis Disturbances in a Cohort of Long-Term Elite Controllers of HIV Infection.
title_full T Cell Homeostasis Disturbances in a Cohort of Long-Term Elite Controllers of HIV Infection.
title_fullStr T Cell Homeostasis Disturbances in a Cohort of Long-Term Elite Controllers of HIV Infection.
title_full_unstemmed T Cell Homeostasis Disturbances in a Cohort of Long-Term Elite Controllers of HIV Infection.
title_sort T Cell Homeostasis Disturbances in a Cohort of Long-Term Elite Controllers of HIV Infection.
dc.creator.none.fl_str_mv Benito, José Miguel
Jiménez-Carretero, Daniel
Restrepo, Clara
Ligos, José M
Valentín-Quiroga, Jaime
Mahillo, Ignacio
Cabello, Alfonso
López-Collazo, Eduardo
Sánchez-Cabo, Fátima
Górgolas, Miguel
Estrada, Vicente
Rallón, Norma
author Benito, José Miguel
author_facet Benito, José Miguel
Jiménez-Carretero, Daniel
Restrepo, Clara
Ligos, José M
Valentín-Quiroga, Jaime
Mahillo, Ignacio
Cabello, Alfonso
López-Collazo, Eduardo
Sánchez-Cabo, Fátima
Górgolas, Miguel
Estrada, Vicente
Rallón, Norma
author_role author
author2 Jiménez-Carretero, Daniel
Restrepo, Clara
Ligos, José M
Valentín-Quiroga, Jaime
Mahillo, Ignacio
Cabello, Alfonso
López-Collazo, Eduardo
Sánchez-Cabo, Fátima
Górgolas, Miguel
Estrada, Vicente
Rallón, Norma
author2_role author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Instituto de Salud Carlos III
Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF)
dc.subject.none.fl_str_mv HIV Infections
Homeostasis
CD4-Positive T-Lymphocytes
CD8-Positive T-Lymphocytes
Humans
Male
Female
Adult
Middle Aged
HIV Long-Term Survivors
HIV-1
Cohort Studies
Viral Load
topic HIV Infections
Homeostasis
CD4-Positive T-Lymphocytes
CD8-Positive T-Lymphocytes
Humans
Male
Female
Adult
Middle Aged
HIV Long-Term Survivors
HIV-1
Cohort Studies
Viral Load
description Elite controllers (ECs) are people living with HIV (PLWH) able to control HIV replication without antiretroviral therapy and have been proposed as a model of a functional HIV cure. Much evidence suggests that this spontaneous control of HIV has a cost in terms of T cell homeostasis alterations. We performed a deep phenotypic study to obtain insight into T cell homeostasis disturbances in ECs maintaining long-term virologic and immunologic control of HIV (long-term elite controllers; LTECs). Forty-seven PLWH were included: 22 LTECs, 15 non-controllers under successful antiretroviral therapy (onART), and 10 non-controllers not receiving ART (offART). Twenty uninfected participants (UCs) were included as a reference. T cell homeostasis was analyzed by spectral flow cytometry and data were analyzed using dimensionality reduction and clustering using R software v3.3.2. Dimensionality reduction and clustering yielded 57 and 54 different CD4 and CD8 T cell clusters, respectively. The offART group showed the highest perturbation of T cell homeostasis, with 18 CD4 clusters and 15 CD8 clusters significantly different from those of UCs. Most of these alterations were reverted in the onART group. Interestingly, LTECs presented several disturbances of T cell homeostasis with 15 CD4 clusters and 13 CD8 clusters different from UC. Moreover, there was a specific profile of T cell homeostasis alterations associated with LTECs, characterized by increases in clusters of naïve T cells, increases in clusters of non-senescent effector CD8 cells, and increases in clusters of central memory CD4 cells. These results demonstrate that, compared to ART-mediated control of HIV, the spontaneous control of HIV is associated with several disturbances in CD4 and CD8 T cell homeostasis. These alterations could be related to the existence of a potent and efficient virus-specific T cell response, and to the ability to halt disease progression by maintaining an adequate pool of CD4 T cells.
publishDate 2024
dc.date.none.fl_str_mv 2024
2024-07-08
2024
2024-05-29
2024
2024-05-29
dc.type.none.fl_str_mv journal article
http://purl.org/coar/resource_type/c_6501
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/20.500.12105/20210
url http://hdl.handle.net/20.500.12105/20210
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
Atribución 4.0 Internacional
http://creativecommons.org/licenses/by/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
Atribución 4.0 Internacional
http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Multidisciplinary Digital Publishing Institute (MDPI)
publisher.none.fl_str_mv Multidisciplinary Digital Publishing Institute (MDPI)
dc.source.none.fl_str_mv reponame:Repisalud
instname:Instituto de Salud Carlos III (ISCIII)
instname_str Instituto de Salud Carlos III (ISCIII)
reponame_str Repisalud
collection Repisalud
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.812429

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