Human CD8+HLA-DR+Regulatory T Cells, similarly to classical CD4+Foxp3+cells, suppress immune responses via PD-1/PD-L1 axis

Autores
Machicote, Andrés Pablo; Belén, Santiago; Baz, Placida; Billordo, Luis Ariel; Fainboim, Leonardo
Año de publicación
2018
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
We have previously identified a human CD8+HLA-DR+ regulatory T cell subset with the ability to suppress proliferation of autologous PBMCs responder cells through cell contact and CTLA-4 co-inhibitory molecule. The present study characterizes the complete phenotype of CD8+HLA-DR+ Treg cells which showed great similarities with classical CD4+ cells expressing forkhead box P3 (FOXP3). The shared features included the expression of programmed cell death protein 1 (PD-1), T-cell immunoreceptor with Ig and ITIM domains (TIGIT), C-C chemokine receptor type 4 and 5 (CCR4 and CCR5), low expression of CD127, and a memory and effector-like phenotype. CD8+HLA-DR+ Treg-induced suppression on CD8+ responder T cells was abrogated by an anti-PD1 neutralizing antibody. Anti-PD-1 did not abrogate the suppressor effect induced on responder CD4+ T cells. In addition, CD8+HLA-DR+ Treg induced a preferential death on responder CD8+ T cells. This effect was not reversed by PD-1 neutralization. After activation, most CD8+HLA-DR+ Treg acquire programmed death-ligand 1 (PD-L1) expression. Interestingly, PD-L1 may induce apoptosis through CD80 expressed on activated CD8+ responder T cells. After PBMCs stimulation, CD8+HLA-DR+ Treg cells showed an increased frequency of IFN-γand TNFα positive cells and higher degranulation. These data strongly argue against CD8+HLA-DR+ Treg being exhausted cells. Overall, the data presented in this study indicate that CD8+HLA-DR+ Treg and CD4+FOXP3+ Treg share phenotypic and functional features, which may provide cues to similar involvements in the control of antitumor immune responses and autoimmunity.
Fil: Machicote, Andrés Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; Argentina
Fil: Belén, Santiago. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; Argentina
Fil: Baz, Placida. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; Argentina
Fil: Billordo, Luis Ariel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; Argentina
Fil: Fainboim, Leonardo. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Microbiología. Cátedra de Microbiología, Parasitología e Inmunología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; Argentina
Materia
ANTI-PD-1
CCR4
CD127
CD8+HLA-DR+
PD-1/PD-L1
REGULATORY T CELLS
TIGIT
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/99445
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/99445
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Human CD8+HLA-DR+Regulatory T Cells, similarly to classical CD4+Foxp3+cells, suppress immune responses via PD-1/PD-L1 axisMachicote, Andrés PabloBelén, SantiagoBaz, PlacidaBillordo, Luis ArielFainboim, LeonardoANTI-PD-1CCR4CD127CD8+HLA-DR+PD-1/PD-L1REGULATORY T CELLSTIGIThttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3We have previously identified a human CD8+HLA-DR+ regulatory T cell subset with the ability to suppress proliferation of autologous PBMCs responder cells through cell contact and CTLA-4 co-inhibitory molecule. The present study characterizes the complete phenotype of CD8+HLA-DR+ Treg cells which showed great similarities with classical CD4+ cells expressing forkhead box P3 (FOXP3). The shared features included the expression of programmed cell death protein 1 (PD-1), T-cell immunoreceptor with Ig and ITIM domains (TIGIT), C-C chemokine receptor type 4 and 5 (CCR4 and CCR5), low expression of CD127, and a memory and effector-like phenotype. CD8+HLA-DR+ Treg-induced suppression on CD8+ responder T cells was abrogated by an anti-PD1 neutralizing antibody. Anti-PD-1 did not abrogate the suppressor effect induced on responder CD4+ T cells. In addition, CD8+HLA-DR+ Treg induced a preferential death on responder CD8+ T cells. This effect was not reversed by PD-1 neutralization. After activation, most CD8+HLA-DR+ Treg acquire programmed death-ligand 1 (PD-L1) expression. Interestingly, PD-L1 may induce apoptosis through CD80 expressed on activated CD8+ responder T cells. After PBMCs stimulation, CD8+HLA-DR+ Treg cells showed an increased frequency of IFN-γand TNFα positive cells and higher degranulation. These data strongly argue against CD8+HLA-DR+ Treg being exhausted cells. Overall, the data presented in this study indicate that CD8+HLA-DR+ Treg and CD4+FOXP3+ Treg share phenotypic and functional features, which may provide cues to similar involvements in the control of antitumor immune responses and autoimmunity.Fil: Machicote, Andrés Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; ArgentinaFil: Belén, Santiago. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; ArgentinaFil: Baz, Placida. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; ArgentinaFil: Billordo, Luis Ariel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; ArgentinaFil: Fainboim, Leonardo. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Microbiología. Cátedra de Microbiología, Parasitología e Inmunología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; ArgentinaFrontiers Media S.A.2018-11info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/99445Machicote, Andrés Pablo; Belén, Santiago; Baz, Placida; Billordo, Luis Ariel; Fainboim, Leonardo; Human CD8+HLA-DR+Regulatory T Cells, similarly to classical CD4+Foxp3+cells, suppress immune responses via PD-1/PD-L1 axis; Frontiers Media S.A.; Frontiers in Immunology; 9; 2788; 11-2018; 1-131664-3224CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.frontiersin.org/articles/10.3389/fimmu.2018.02788info:eu-repo/semantics/altIdentifier/doi/10.3389/fimmu.2018.02788info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:02:47Zoai:ri.conicet.gov.ar:11336/99445instacron: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:34982025-09-29 10:02:47.333CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Human CD8+HLA-DR+Regulatory T Cells, similarly to classical CD4+Foxp3+cells, suppress immune responses via PD-1/PD-L1 axis
title Human CD8+HLA-DR+Regulatory T Cells, similarly to classical CD4+Foxp3+cells, suppress immune responses via PD-1/PD-L1 axis
spellingShingle Human CD8+HLA-DR+Regulatory T Cells, similarly to classical CD4+Foxp3+cells, suppress immune responses via PD-1/PD-L1 axis
Machicote, Andrés Pablo
ANTI-PD-1
CCR4
CD127
CD8+HLA-DR+
PD-1/PD-L1
REGULATORY T CELLS
TIGIT
title_short Human CD8+HLA-DR+Regulatory T Cells, similarly to classical CD4+Foxp3+cells, suppress immune responses via PD-1/PD-L1 axis
title_full Human CD8+HLA-DR+Regulatory T Cells, similarly to classical CD4+Foxp3+cells, suppress immune responses via PD-1/PD-L1 axis
title_fullStr Human CD8+HLA-DR+Regulatory T Cells, similarly to classical CD4+Foxp3+cells, suppress immune responses via PD-1/PD-L1 axis
title_full_unstemmed Human CD8+HLA-DR+Regulatory T Cells, similarly to classical CD4+Foxp3+cells, suppress immune responses via PD-1/PD-L1 axis
title_sort Human CD8+HLA-DR+Regulatory T Cells, similarly to classical CD4+Foxp3+cells, suppress immune responses via PD-1/PD-L1 axis
dc.creator.none.fl_str_mv Machicote, Andrés Pablo
Belén, Santiago
Baz, Placida
Billordo, Luis Ariel
Fainboim, Leonardo
author Machicote, Andrés Pablo
author_facet Machicote, Andrés Pablo
Belén, Santiago
Baz, Placida
Billordo, Luis Ariel
Fainboim, Leonardo
author_role author
author2 Belén, Santiago
Baz, Placida
Billordo, Luis Ariel
Fainboim, Leonardo
author2_role author
author
author
author
dc.subject.none.fl_str_mv ANTI-PD-1
CCR4
CD127
CD8+HLA-DR+
PD-1/PD-L1
REGULATORY T CELLS
TIGIT
topic ANTI-PD-1
CCR4
CD127
CD8+HLA-DR+
PD-1/PD-L1
REGULATORY T CELLS
TIGIT
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv We have previously identified a human CD8+HLA-DR+ regulatory T cell subset with the ability to suppress proliferation of autologous PBMCs responder cells through cell contact and CTLA-4 co-inhibitory molecule. The present study characterizes the complete phenotype of CD8+HLA-DR+ Treg cells which showed great similarities with classical CD4+ cells expressing forkhead box P3 (FOXP3). The shared features included the expression of programmed cell death protein 1 (PD-1), T-cell immunoreceptor with Ig and ITIM domains (TIGIT), C-C chemokine receptor type 4 and 5 (CCR4 and CCR5), low expression of CD127, and a memory and effector-like phenotype. CD8+HLA-DR+ Treg-induced suppression on CD8+ responder T cells was abrogated by an anti-PD1 neutralizing antibody. Anti-PD-1 did not abrogate the suppressor effect induced on responder CD4+ T cells. In addition, CD8+HLA-DR+ Treg induced a preferential death on responder CD8+ T cells. This effect was not reversed by PD-1 neutralization. After activation, most CD8+HLA-DR+ Treg acquire programmed death-ligand 1 (PD-L1) expression. Interestingly, PD-L1 may induce apoptosis through CD80 expressed on activated CD8+ responder T cells. After PBMCs stimulation, CD8+HLA-DR+ Treg cells showed an increased frequency of IFN-γand TNFα positive cells and higher degranulation. These data strongly argue against CD8+HLA-DR+ Treg being exhausted cells. Overall, the data presented in this study indicate that CD8+HLA-DR+ Treg and CD4+FOXP3+ Treg share phenotypic and functional features, which may provide cues to similar involvements in the control of antitumor immune responses and autoimmunity.
Fil: Machicote, Andrés Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; Argentina
Fil: Belén, Santiago. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; Argentina
Fil: Baz, Placida. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; Argentina
Fil: Billordo, Luis Ariel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; Argentina
Fil: Fainboim, Leonardo. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Microbiología. Cátedra de Microbiología, Parasitología e Inmunología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; Argentina
description We have previously identified a human CD8+HLA-DR+ regulatory T cell subset with the ability to suppress proliferation of autologous PBMCs responder cells through cell contact and CTLA-4 co-inhibitory molecule. The present study characterizes the complete phenotype of CD8+HLA-DR+ Treg cells which showed great similarities with classical CD4+ cells expressing forkhead box P3 (FOXP3). The shared features included the expression of programmed cell death protein 1 (PD-1), T-cell immunoreceptor with Ig and ITIM domains (TIGIT), C-C chemokine receptor type 4 and 5 (CCR4 and CCR5), low expression of CD127, and a memory and effector-like phenotype. CD8+HLA-DR+ Treg-induced suppression on CD8+ responder T cells was abrogated by an anti-PD1 neutralizing antibody. Anti-PD-1 did not abrogate the suppressor effect induced on responder CD4+ T cells. In addition, CD8+HLA-DR+ Treg induced a preferential death on responder CD8+ T cells. This effect was not reversed by PD-1 neutralization. After activation, most CD8+HLA-DR+ Treg acquire programmed death-ligand 1 (PD-L1) expression. Interestingly, PD-L1 may induce apoptosis through CD80 expressed on activated CD8+ responder T cells. After PBMCs stimulation, CD8+HLA-DR+ Treg cells showed an increased frequency of IFN-γand TNFα positive cells and higher degranulation. These data strongly argue against CD8+HLA-DR+ Treg being exhausted cells. Overall, the data presented in this study indicate that CD8+HLA-DR+ Treg and CD4+FOXP3+ Treg share phenotypic and functional features, which may provide cues to similar involvements in the control of antitumor immune responses and autoimmunity.
publishDate 2018
dc.date.none.fl_str_mv 2018-11
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/11336/99445
Machicote, Andrés Pablo; Belén, Santiago; Baz, Placida; Billordo, Luis Ariel; Fainboim, Leonardo; Human CD8+HLA-DR+Regulatory T Cells, similarly to classical CD4+Foxp3+cells, suppress immune responses via PD-1/PD-L1 axis; Frontiers Media S.A.; Frontiers in Immunology; 9; 2788; 11-2018; 1-13
1664-3224
CONICET Digital
CONICET
url http://hdl.handle.net/11336/99445
identifier_str_mv Machicote, Andrés Pablo; Belén, Santiago; Baz, Placida; Billordo, Luis Ariel; Fainboim, Leonardo; Human CD8+HLA-DR+Regulatory T Cells, similarly to classical CD4+Foxp3+cells, suppress immune responses via PD-1/PD-L1 axis; Frontiers Media S.A.; Frontiers in Immunology; 9; 2788; 11-2018; 1-13
1664-3224
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.frontiersin.org/articles/10.3389/fimmu.2018.02788
info:eu-repo/semantics/altIdentifier/doi/10.3389/fimmu.2018.02788
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Frontiers Media S.A.
publisher.none.fl_str_mv Frontiers Media S.A.
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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score 13.070432

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