CD4+ T cells with an activated and exhausted phenotype distinguish immunodeficiency during aviremic HIV-2 infection

Autores
Buggert, Marcus; Frederiksen, Juliet; Lund, Ole; Betts, Michael R.; Biague, Antonio; Nielsen, Morten; Tauriainen, Johanna; Norrgren, Hans; Medstrand, Patrik; SWEGUB CORE group; Karlsson, Annika C.; Jansson, Marianne
Año de publicación
2016
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Objective: HIV type 2 (HIV-2) represents an attenuated form of HIV, in which many infected individuals remain 'aviremic' without antiretroviral therapy. However, aviremic HIV-2 disease progression exists, and in the current study, we therefore aimed to examine if specific pathological characteristics of CD4 T cells are linked to such outcome. Design: HIV-seronegative (n = 25), HIV type 1 (HIV-1) (n = 33), HIV-2 (n = 39, of whom 26 were aviremic), and HIV-1/2 dually (HIV-D) (n = 13)-infected study participants were enrolled from an occupational cohort in Guinea-Bissau. Methods: CD4+ T-cell differentiation, activation, exhaustion, senescence, and transcription factors were assessed by polychromatic flow cytometry. Multidimensional clustering bioinformatic tools were used to identify CD4+ T-cell subpopulations linked to infection type and disease stage. Results: HIV-2-infected individuals had early and late-differentiated CD4+ T-cell clusters with lower activation (CD38+HLA-DR+) and exhaustion programmed death-1 (PD-1) than HIV-1 and HIV-D-infected individuals. We also noted that aviremic HIV-2-infected individuals possessed fewer individuals. CD4+ T cells with pathological signs compared to other HIV-infected groups. Still, compared to HIV-seronegative individuals, aviremic HIV-2-infected individuals had T-bet+ CD4+ T cells that showed elevated immune activation/exhaustion, and particularly the frequencies of PD-1+ cells were associated with a suboptimal percentage of CD4+ T cells. Conclusion: Increased frequencies of CD4+ T cells with an activated/exhausted phenotype correlate with exacerbated immunodeficiency in aviremic HIV-2-infected individuals. Thus, these findings encourage studies on the introduction of antiretroviral therapy also to individuals with aviremic HIV-2 infection.
Fil: Buggert, Marcus. Karolinska Institutet; Suecia. University of Pennsylvania; Estados Unidos
Fil: Frederiksen, Juliet. Technical University of Denmark; Dinamarca
Fil: Lund, Ole. Technical University of Denmark; Dinamarca
Fil: Betts, Michael R.. University of Pennsylvania; Estados Unidos
Fil: Biague, Antonio. National Public Health Laboratory; Guinea
Fil: Nielsen, Morten. Technical University of Denmark; Dinamarca. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús). Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús); Argentina
Fil: Tauriainen, Johanna. Karolinska Institutet; Suecia
Fil: Norrgren, Hans. Lund University; Suecia
Fil: Medstrand, Patrik. Lund University; Suecia
Fil: SWEGUB CORE group. No especifica;
Fil: Karlsson, Annika C.. Karolinska Institutet; Suecia
Fil: Jansson, Marianne. Lund University; Suecia. Karolinska Institutet; Suecia
Materia
ACTIVATION
CD4+ T CELLS
EXHAUSTION
HIV-1
HIV-2
IMMUNODEFICIENCY
VIREMIA
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/54912

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oai_identifier_str oai:ri.conicet.gov.ar:11336/54912
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling CD4+ T cells with an activated and exhausted phenotype distinguish immunodeficiency during aviremic HIV-2 infectionBuggert, MarcusFrederiksen, JulietLund, OleBetts, Michael R.Biague, AntonioNielsen, MortenTauriainen, JohannaNorrgren, HansMedstrand, PatrikSWEGUB CORE groupKarlsson, Annika C.Jansson, MarianneACTIVATIONCD4+ T CELLSEXHAUSTIONHIV-1HIV-2IMMUNODEFICIENCYVIREMIAhttps://purl.org/becyt/ford/3.3https://purl.org/becyt/ford/3Objective: HIV type 2 (HIV-2) represents an attenuated form of HIV, in which many infected individuals remain 'aviremic' without antiretroviral therapy. However, aviremic HIV-2 disease progression exists, and in the current study, we therefore aimed to examine if specific pathological characteristics of CD4 T cells are linked to such outcome. Design: HIV-seronegative (n = 25), HIV type 1 (HIV-1) (n = 33), HIV-2 (n = 39, of whom 26 were aviremic), and HIV-1/2 dually (HIV-D) (n = 13)-infected study participants were enrolled from an occupational cohort in Guinea-Bissau. Methods: CD4+ T-cell differentiation, activation, exhaustion, senescence, and transcription factors were assessed by polychromatic flow cytometry. Multidimensional clustering bioinformatic tools were used to identify CD4+ T-cell subpopulations linked to infection type and disease stage. Results: HIV-2-infected individuals had early and late-differentiated CD4+ T-cell clusters with lower activation (CD38+HLA-DR+) and exhaustion programmed death-1 (PD-1) than HIV-1 and HIV-D-infected individuals. We also noted that aviremic HIV-2-infected individuals possessed fewer individuals. CD4+ T cells with pathological signs compared to other HIV-infected groups. Still, compared to HIV-seronegative individuals, aviremic HIV-2-infected individuals had T-bet+ CD4+ T cells that showed elevated immune activation/exhaustion, and particularly the frequencies of PD-1+ cells were associated with a suboptimal percentage of CD4+ T cells. Conclusion: Increased frequencies of CD4+ T cells with an activated/exhausted phenotype correlate with exacerbated immunodeficiency in aviremic HIV-2-infected individuals. Thus, these findings encourage studies on the introduction of antiretroviral therapy also to individuals with aviremic HIV-2 infection.Fil: Buggert, Marcus. Karolinska Institutet; Suecia. University of Pennsylvania; Estados UnidosFil: Frederiksen, Juliet. Technical University of Denmark; DinamarcaFil: Lund, Ole. Technical University of Denmark; DinamarcaFil: Betts, Michael R.. University of Pennsylvania; Estados UnidosFil: Biague, Antonio. National Public Health Laboratory; GuineaFil: Nielsen, Morten. Technical University of Denmark; Dinamarca. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús). Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús); ArgentinaFil: Tauriainen, Johanna. Karolinska Institutet; SueciaFil: Norrgren, Hans. Lund University; SueciaFil: Medstrand, Patrik. Lund University; SueciaFil: SWEGUB CORE group. No especifica;Fil: Karlsson, Annika C.. Karolinska Institutet; SueciaFil: Jansson, Marianne. Lund University; Suecia. Karolinska Institutet; SueciaLippincott Williams2016-10info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/54912Buggert, Marcus; Frederiksen, Juliet; Lund, Ole; Betts, Michael R.; Biague, Antonio; et al.; CD4+ T cells with an activated and exhausted phenotype distinguish immunodeficiency during aviremic HIV-2 infection; Lippincott Williams; Aids; 30; 16; 10-2016; 2415-24260269-9370CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1097/QAD.0000000000001223info:eu-repo/semantics/altIdentifier/url/https://journals.lww.com/aidsonline/Fulltext/2016/10230/CD4__T_cells_with_an_activated_and_exhausted.3.aspxinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-15T15:42:22Zoai:ri.conicet.gov.ar:11336/54912instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-10-15 15:42:22.994CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv CD4+ T cells with an activated and exhausted phenotype distinguish immunodeficiency during aviremic HIV-2 infection
title CD4+ T cells with an activated and exhausted phenotype distinguish immunodeficiency during aviremic HIV-2 infection
spellingShingle CD4+ T cells with an activated and exhausted phenotype distinguish immunodeficiency during aviremic HIV-2 infection
Buggert, Marcus
ACTIVATION
CD4+ T CELLS
EXHAUSTION
HIV-1
HIV-2
IMMUNODEFICIENCY
VIREMIA
title_short CD4+ T cells with an activated and exhausted phenotype distinguish immunodeficiency during aviremic HIV-2 infection
title_full CD4+ T cells with an activated and exhausted phenotype distinguish immunodeficiency during aviremic HIV-2 infection
title_fullStr CD4+ T cells with an activated and exhausted phenotype distinguish immunodeficiency during aviremic HIV-2 infection
title_full_unstemmed CD4+ T cells with an activated and exhausted phenotype distinguish immunodeficiency during aviremic HIV-2 infection
title_sort CD4+ T cells with an activated and exhausted phenotype distinguish immunodeficiency during aviremic HIV-2 infection
dc.creator.none.fl_str_mv Buggert, Marcus
Frederiksen, Juliet
Lund, Ole
Betts, Michael R.
Biague, Antonio
Nielsen, Morten
Tauriainen, Johanna
Norrgren, Hans
Medstrand, Patrik
SWEGUB CORE group
Karlsson, Annika C.
Jansson, Marianne
author Buggert, Marcus
author_facet Buggert, Marcus
Frederiksen, Juliet
Lund, Ole
Betts, Michael R.
Biague, Antonio
Nielsen, Morten
Tauriainen, Johanna
Norrgren, Hans
Medstrand, Patrik
SWEGUB CORE group
Karlsson, Annika C.
Jansson, Marianne
author_role author
author2 Frederiksen, Juliet
Lund, Ole
Betts, Michael R.
Biague, Antonio
Nielsen, Morten
Tauriainen, Johanna
Norrgren, Hans
Medstrand, Patrik
SWEGUB CORE group
Karlsson, Annika C.
Jansson, Marianne
author2_role author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv ACTIVATION
CD4+ T CELLS
EXHAUSTION
HIV-1
HIV-2
IMMUNODEFICIENCY
VIREMIA
topic ACTIVATION
CD4+ T CELLS
EXHAUSTION
HIV-1
HIV-2
IMMUNODEFICIENCY
VIREMIA
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.3
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Objective: HIV type 2 (HIV-2) represents an attenuated form of HIV, in which many infected individuals remain 'aviremic' without antiretroviral therapy. However, aviremic HIV-2 disease progression exists, and in the current study, we therefore aimed to examine if specific pathological characteristics of CD4 T cells are linked to such outcome. Design: HIV-seronegative (n = 25), HIV type 1 (HIV-1) (n = 33), HIV-2 (n = 39, of whom 26 were aviremic), and HIV-1/2 dually (HIV-D) (n = 13)-infected study participants were enrolled from an occupational cohort in Guinea-Bissau. Methods: CD4+ T-cell differentiation, activation, exhaustion, senescence, and transcription factors were assessed by polychromatic flow cytometry. Multidimensional clustering bioinformatic tools were used to identify CD4+ T-cell subpopulations linked to infection type and disease stage. Results: HIV-2-infected individuals had early and late-differentiated CD4+ T-cell clusters with lower activation (CD38+HLA-DR+) and exhaustion programmed death-1 (PD-1) than HIV-1 and HIV-D-infected individuals. We also noted that aviremic HIV-2-infected individuals possessed fewer individuals. CD4+ T cells with pathological signs compared to other HIV-infected groups. Still, compared to HIV-seronegative individuals, aviremic HIV-2-infected individuals had T-bet+ CD4+ T cells that showed elevated immune activation/exhaustion, and particularly the frequencies of PD-1+ cells were associated with a suboptimal percentage of CD4+ T cells. Conclusion: Increased frequencies of CD4+ T cells with an activated/exhausted phenotype correlate with exacerbated immunodeficiency in aviremic HIV-2-infected individuals. Thus, these findings encourage studies on the introduction of antiretroviral therapy also to individuals with aviremic HIV-2 infection.
Fil: Buggert, Marcus. Karolinska Institutet; Suecia. University of Pennsylvania; Estados Unidos
Fil: Frederiksen, Juliet. Technical University of Denmark; Dinamarca
Fil: Lund, Ole. Technical University of Denmark; Dinamarca
Fil: Betts, Michael R.. University of Pennsylvania; Estados Unidos
Fil: Biague, Antonio. National Public Health Laboratory; Guinea
Fil: Nielsen, Morten. Technical University of Denmark; Dinamarca. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús). Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús); Argentina
Fil: Tauriainen, Johanna. Karolinska Institutet; Suecia
Fil: Norrgren, Hans. Lund University; Suecia
Fil: Medstrand, Patrik. Lund University; Suecia
Fil: SWEGUB CORE group. No especifica;
Fil: Karlsson, Annika C.. Karolinska Institutet; Suecia
Fil: Jansson, Marianne. Lund University; Suecia. Karolinska Institutet; Suecia
description Objective: HIV type 2 (HIV-2) represents an attenuated form of HIV, in which many infected individuals remain 'aviremic' without antiretroviral therapy. However, aviremic HIV-2 disease progression exists, and in the current study, we therefore aimed to examine if specific pathological characteristics of CD4 T cells are linked to such outcome. Design: HIV-seronegative (n = 25), HIV type 1 (HIV-1) (n = 33), HIV-2 (n = 39, of whom 26 were aviremic), and HIV-1/2 dually (HIV-D) (n = 13)-infected study participants were enrolled from an occupational cohort in Guinea-Bissau. Methods: CD4+ T-cell differentiation, activation, exhaustion, senescence, and transcription factors were assessed by polychromatic flow cytometry. Multidimensional clustering bioinformatic tools were used to identify CD4+ T-cell subpopulations linked to infection type and disease stage. Results: HIV-2-infected individuals had early and late-differentiated CD4+ T-cell clusters with lower activation (CD38+HLA-DR+) and exhaustion programmed death-1 (PD-1) than HIV-1 and HIV-D-infected individuals. We also noted that aviremic HIV-2-infected individuals possessed fewer individuals. CD4+ T cells with pathological signs compared to other HIV-infected groups. Still, compared to HIV-seronegative individuals, aviremic HIV-2-infected individuals had T-bet+ CD4+ T cells that showed elevated immune activation/exhaustion, and particularly the frequencies of PD-1+ cells were associated with a suboptimal percentage of CD4+ T cells. Conclusion: Increased frequencies of CD4+ T cells with an activated/exhausted phenotype correlate with exacerbated immunodeficiency in aviremic HIV-2-infected individuals. Thus, these findings encourage studies on the introduction of antiretroviral therapy also to individuals with aviremic HIV-2 infection.
publishDate 2016
dc.date.none.fl_str_mv 2016-10
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/54912
Buggert, Marcus; Frederiksen, Juliet; Lund, Ole; Betts, Michael R.; Biague, Antonio; et al.; CD4+ T cells with an activated and exhausted phenotype distinguish immunodeficiency during aviremic HIV-2 infection; Lippincott Williams; Aids; 30; 16; 10-2016; 2415-2426
0269-9370
CONICET Digital
CONICET
url http://hdl.handle.net/11336/54912
identifier_str_mv Buggert, Marcus; Frederiksen, Juliet; Lund, Ole; Betts, Michael R.; Biague, Antonio; et al.; CD4+ T cells with an activated and exhausted phenotype distinguish immunodeficiency during aviremic HIV-2 infection; Lippincott Williams; Aids; 30; 16; 10-2016; 2415-2426
0269-9370
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1097/QAD.0000000000001223
info:eu-repo/semantics/altIdentifier/url/https://journals.lww.com/aidsonline/Fulltext/2016/10230/CD4__T_cells_with_an_activated_and_exhausted.3.aspx
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Lippincott Williams
publisher.none.fl_str_mv Lippincott Williams
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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