Inhibitory Receptor Expression on T Cells as a Marker of Disease Activity and Target to Regulate Effector Cellular Responses in Rheumatoid Arthritis

Autores
Onofrio, Luisina Inés; Zacca, Estefanía; Ferrero, Paola Virginia; Acosta, Cristina; Mussano, Eduardo; Onetti, Laura; Cadile, Isaac; Gazzoni, M. Victoria; Jurado, Raúl; Tosello Boari, Jimena; Ramello, María Cecilia; Montes, Carolina Lucia; Gruppi, Adriana; Acosta Rodriguez, Eva Virginia
Año de publicación
2018
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Objective: Inhibitory receptors are essential for the regulation of effector immune responses and may play critical roles in autoimmune diseases. We evaluated whether inhibitory receptor expression on T cells from patients with rheumatoid arthritis (RA) were correlated with immune activation, disease activity, and response to treatment, as well as whether inhibitory receptor–mediated pathways were functional. Methods: Using flow cytometry, we performed extensive phenotypic and functional evaluation of CD4+ and CD8+ T cells from the blood and synovial fluid (SF) of RA patients ex vivo and after culture. The relationship of each parameter with the Disease Activity Score in 28 joints using the erythrocyte sedimentation rate (DAS28-ESR) and response to treatment was examined. Results: In RA patients with low levels of T cell activation, inhibitory receptor expression showed an inverse relationship with the DAS28-ESR. The frequency of T cells expressing multiple inhibitory receptors was reduced in untreated RA patients but returned to normal levels in treated patients. RA patients who responded to treatment showed an augmented frequency of inhibitory receptor–expressing T cells that correlated with reduced inflammatory cytokine production in comparison to nonresponders. Higher frequencies of effector and memory T cells that expressed multiple inhibitory receptors were seen in SF than in peripheral blood. Notably, inhibitory pathways were operative in blood and synovial T cells from all RA patients, although cells from nonresponder patients were less sensitive to inhibition. Conclusion: Inhibitory receptor expression on T cells from RA patients is inversely correlated with effector T cell function and disease activity and may predict response to treatment. Furthermore, different inhibitory pathways are functional and cooperatively suppress synovial T cells, providing a rationale for new treatment strategies to regulate acute local inflammation.
Fil: Onofrio, Luisina Inés. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina. Universidad Nacional de Córdoba. Facultad de Medicina. Hospital Nacional de Clínicas; Argentina
Fil: Zacca, Estefanía. Universidad Nacional de Córdoba. Facultad de Medicina. Hospital Nacional de Clínicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Fil: Ferrero, Paola Virginia. Universidad Nacional de Córdoba. Facultad de Medicina. Hospital Nacional de Clínicas; Argentina
Fil: Acosta, Cristina. Universidad Nacional de Córdoba. Facultad de Medicina. Hospital Nacional de Clínicas; Argentina
Fil: Mussano, Eduardo. Universidad Nacional de Córdoba. Facultad de Medicina. Hospital Nacional de Clínicas; Argentina
Fil: Onetti, Laura. Universidad Nacional de Córdoba. Facultad de Medicina. Hospital Nacional de Clínicas; Argentina
Fil: Cadile, Isaac. Universidad Nacional de Córdoba. Facultad de Medicina. Hospital Nacional de Clínicas; Argentina
Fil: Gazzoni, M. Victoria. Universidad Nacional de Córdoba. Facultad de Medicina. Hospital Nacional de Clínicas; Argentina
Fil: Jurado, Raúl. Universidad Nacional de Córdoba. Facultad de Medicina. Hospital Nacional de Clínicas; Argentina
Fil: Tosello Boari, Jimena. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Fil: Ramello, María Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Fil: Montes, Carolina Lucia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Fil: Gruppi, Adriana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Fil: Acosta Rodriguez, Eva Virginia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Materia
RHEUMAOTID ARTHRITIS
INHIBITORY RECEPTORS
T CELLS
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:11336/95902
Acceder
id CONICETDig_f0d6667f0e24f327a27fe30ed55f03cf
oai_identifier_str oai:ri.conicet.gov.ar:11336/95902
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Inhibitory Receptor Expression on T Cells as a Marker of Disease Activity and Target to Regulate Effector Cellular Responses in Rheumatoid ArthritisOnofrio, Luisina InésZacca, EstefaníaFerrero, Paola VirginiaAcosta, CristinaMussano, EduardoOnetti, LauraCadile, IsaacGazzoni, M. VictoriaJurado, RaúlTosello Boari, JimenaRamello, María CeciliaMontes, Carolina LuciaGruppi, AdrianaAcosta Rodriguez, Eva VirginiaRHEUMAOTID ARTHRITISINHIBITORY RECEPTORST CELLShttps://purl.org/becyt/ford/3.2https://purl.org/becyt/ford/3Objective: Inhibitory receptors are essential for the regulation of effector immune responses and may play critical roles in autoimmune diseases. We evaluated whether inhibitory receptor expression on T cells from patients with rheumatoid arthritis (RA) were correlated with immune activation, disease activity, and response to treatment, as well as whether inhibitory receptor–mediated pathways were functional. Methods: Using flow cytometry, we performed extensive phenotypic and functional evaluation of CD4+ and CD8+ T cells from the blood and synovial fluid (SF) of RA patients ex vivo and after culture. The relationship of each parameter with the Disease Activity Score in 28 joints using the erythrocyte sedimentation rate (DAS28-ESR) and response to treatment was examined. Results: In RA patients with low levels of T cell activation, inhibitory receptor expression showed an inverse relationship with the DAS28-ESR. The frequency of T cells expressing multiple inhibitory receptors was reduced in untreated RA patients but returned to normal levels in treated patients. RA patients who responded to treatment showed an augmented frequency of inhibitory receptor–expressing T cells that correlated with reduced inflammatory cytokine production in comparison to nonresponders. Higher frequencies of effector and memory T cells that expressed multiple inhibitory receptors were seen in SF than in peripheral blood. Notably, inhibitory pathways were operative in blood and synovial T cells from all RA patients, although cells from nonresponder patients were less sensitive to inhibition. Conclusion: Inhibitory receptor expression on T cells from RA patients is inversely correlated with effector T cell function and disease activity and may predict response to treatment. Furthermore, different inhibitory pathways are functional and cooperatively suppress synovial T cells, providing a rationale for new treatment strategies to regulate acute local inflammation.Fil: Onofrio, Luisina Inés. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina. Universidad Nacional de Córdoba. Facultad de Medicina. Hospital Nacional de Clínicas; ArgentinaFil: Zacca, Estefanía. Universidad Nacional de Córdoba. Facultad de Medicina. Hospital Nacional de Clínicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Ferrero, Paola Virginia. Universidad Nacional de Córdoba. Facultad de Medicina. Hospital Nacional de Clínicas; ArgentinaFil: Acosta, Cristina. Universidad Nacional de Córdoba. Facultad de Medicina. Hospital Nacional de Clínicas; ArgentinaFil: Mussano, Eduardo. Universidad Nacional de Córdoba. Facultad de Medicina. Hospital Nacional de Clínicas; ArgentinaFil: Onetti, Laura. Universidad Nacional de Córdoba. Facultad de Medicina. Hospital Nacional de Clínicas; ArgentinaFil: Cadile, Isaac. Universidad Nacional de Córdoba. Facultad de Medicina. Hospital Nacional de Clínicas; ArgentinaFil: Gazzoni, M. Victoria. Universidad Nacional de Córdoba. Facultad de Medicina. Hospital Nacional de Clínicas; ArgentinaFil: Jurado, Raúl. Universidad Nacional de Córdoba. Facultad de Medicina. Hospital Nacional de Clínicas; ArgentinaFil: Tosello Boari, Jimena. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Ramello, María Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Montes, Carolina Lucia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Gruppi, Adriana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Acosta Rodriguez, Eva Virginia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaJohn Wiley & Sons Inc2018-09info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/95902Onofrio, Luisina Inés; Zacca, Estefanía; Ferrero, Paola Virginia; Acosta, Cristina; Mussano, Eduardo; et al.; Inhibitory Receptor Expression on T Cells as a Marker of Disease Activity and Target to Regulate Effector Cellular Responses in Rheumatoid Arthritis; John Wiley & Sons Inc; Arthritis and Rheumatology; 70; 9; 9-2018; 1429-14392326-5205CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1002/art.40521info:eu-repo/semantics/altIdentifier/url/https://onlinelibrary.wiley.com/doi/full/10.1002/art.40521info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:58:52Zoai:ri.conicet.gov.ar:11336/95902instacron: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 09:58:52.85CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Inhibitory Receptor Expression on T Cells as a Marker of Disease Activity and Target to Regulate Effector Cellular Responses in Rheumatoid Arthritis
title Inhibitory Receptor Expression on T Cells as a Marker of Disease Activity and Target to Regulate Effector Cellular Responses in Rheumatoid Arthritis
spellingShingle Inhibitory Receptor Expression on T Cells as a Marker of Disease Activity and Target to Regulate Effector Cellular Responses in Rheumatoid Arthritis
Onofrio, Luisina Inés
RHEUMAOTID ARTHRITIS
INHIBITORY RECEPTORS
T CELLS
title_short Inhibitory Receptor Expression on T Cells as a Marker of Disease Activity and Target to Regulate Effector Cellular Responses in Rheumatoid Arthritis
title_full Inhibitory Receptor Expression on T Cells as a Marker of Disease Activity and Target to Regulate Effector Cellular Responses in Rheumatoid Arthritis
title_fullStr Inhibitory Receptor Expression on T Cells as a Marker of Disease Activity and Target to Regulate Effector Cellular Responses in Rheumatoid Arthritis
title_full_unstemmed Inhibitory Receptor Expression on T Cells as a Marker of Disease Activity and Target to Regulate Effector Cellular Responses in Rheumatoid Arthritis
title_sort Inhibitory Receptor Expression on T Cells as a Marker of Disease Activity and Target to Regulate Effector Cellular Responses in Rheumatoid Arthritis
dc.creator.none.fl_str_mv Onofrio, Luisina Inés
Zacca, Estefanía
Ferrero, Paola Virginia
Acosta, Cristina
Mussano, Eduardo
Onetti, Laura
Cadile, Isaac
Gazzoni, M. Victoria
Jurado, Raúl
Tosello Boari, Jimena
Ramello, María Cecilia
Montes, Carolina Lucia
Gruppi, Adriana
Acosta Rodriguez, Eva Virginia
author Onofrio, Luisina Inés
author_facet Onofrio, Luisina Inés
Zacca, Estefanía
Ferrero, Paola Virginia
Acosta, Cristina
Mussano, Eduardo
Onetti, Laura
Cadile, Isaac
Gazzoni, M. Victoria
Jurado, Raúl
Tosello Boari, Jimena
Ramello, María Cecilia
Montes, Carolina Lucia
Gruppi, Adriana
Acosta Rodriguez, Eva Virginia
author_role author
author2 Zacca, Estefanía
Ferrero, Paola Virginia
Acosta, Cristina
Mussano, Eduardo
Onetti, Laura
Cadile, Isaac
Gazzoni, M. Victoria
Jurado, Raúl
Tosello Boari, Jimena
Ramello, María Cecilia
Montes, Carolina Lucia
Gruppi, Adriana
Acosta Rodriguez, Eva Virginia
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv RHEUMAOTID ARTHRITIS
INHIBITORY RECEPTORS
T CELLS
topic RHEUMAOTID ARTHRITIS
INHIBITORY RECEPTORS
T CELLS
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.2
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Objective: Inhibitory receptors are essential for the regulation of effector immune responses and may play critical roles in autoimmune diseases. We evaluated whether inhibitory receptor expression on T cells from patients with rheumatoid arthritis (RA) were correlated with immune activation, disease activity, and response to treatment, as well as whether inhibitory receptor–mediated pathways were functional. Methods: Using flow cytometry, we performed extensive phenotypic and functional evaluation of CD4+ and CD8+ T cells from the blood and synovial fluid (SF) of RA patients ex vivo and after culture. The relationship of each parameter with the Disease Activity Score in 28 joints using the erythrocyte sedimentation rate (DAS28-ESR) and response to treatment was examined. Results: In RA patients with low levels of T cell activation, inhibitory receptor expression showed an inverse relationship with the DAS28-ESR. The frequency of T cells expressing multiple inhibitory receptors was reduced in untreated RA patients but returned to normal levels in treated patients. RA patients who responded to treatment showed an augmented frequency of inhibitory receptor–expressing T cells that correlated with reduced inflammatory cytokine production in comparison to nonresponders. Higher frequencies of effector and memory T cells that expressed multiple inhibitory receptors were seen in SF than in peripheral blood. Notably, inhibitory pathways were operative in blood and synovial T cells from all RA patients, although cells from nonresponder patients were less sensitive to inhibition. Conclusion: Inhibitory receptor expression on T cells from RA patients is inversely correlated with effector T cell function and disease activity and may predict response to treatment. Furthermore, different inhibitory pathways are functional and cooperatively suppress synovial T cells, providing a rationale for new treatment strategies to regulate acute local inflammation.
Fil: Onofrio, Luisina Inés. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina. Universidad Nacional de Córdoba. Facultad de Medicina. Hospital Nacional de Clínicas; Argentina
Fil: Zacca, Estefanía. Universidad Nacional de Córdoba. Facultad de Medicina. Hospital Nacional de Clínicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Fil: Ferrero, Paola Virginia. Universidad Nacional de Córdoba. Facultad de Medicina. Hospital Nacional de Clínicas; Argentina
Fil: Acosta, Cristina. Universidad Nacional de Córdoba. Facultad de Medicina. Hospital Nacional de Clínicas; Argentina
Fil: Mussano, Eduardo. Universidad Nacional de Córdoba. Facultad de Medicina. Hospital Nacional de Clínicas; Argentina
Fil: Onetti, Laura. Universidad Nacional de Córdoba. Facultad de Medicina. Hospital Nacional de Clínicas; Argentina
Fil: Cadile, Isaac. Universidad Nacional de Córdoba. Facultad de Medicina. Hospital Nacional de Clínicas; Argentina
Fil: Gazzoni, M. Victoria. Universidad Nacional de Córdoba. Facultad de Medicina. Hospital Nacional de Clínicas; Argentina
Fil: Jurado, Raúl. Universidad Nacional de Córdoba. Facultad de Medicina. Hospital Nacional de Clínicas; Argentina
Fil: Tosello Boari, Jimena. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Fil: Ramello, María Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Fil: Montes, Carolina Lucia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Fil: Gruppi, Adriana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Fil: Acosta Rodriguez, Eva Virginia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
description Objective: Inhibitory receptors are essential for the regulation of effector immune responses and may play critical roles in autoimmune diseases. We evaluated whether inhibitory receptor expression on T cells from patients with rheumatoid arthritis (RA) were correlated with immune activation, disease activity, and response to treatment, as well as whether inhibitory receptor–mediated pathways were functional. Methods: Using flow cytometry, we performed extensive phenotypic and functional evaluation of CD4+ and CD8+ T cells from the blood and synovial fluid (SF) of RA patients ex vivo and after culture. The relationship of each parameter with the Disease Activity Score in 28 joints using the erythrocyte sedimentation rate (DAS28-ESR) and response to treatment was examined. Results: In RA patients with low levels of T cell activation, inhibitory receptor expression showed an inverse relationship with the DAS28-ESR. The frequency of T cells expressing multiple inhibitory receptors was reduced in untreated RA patients but returned to normal levels in treated patients. RA patients who responded to treatment showed an augmented frequency of inhibitory receptor–expressing T cells that correlated with reduced inflammatory cytokine production in comparison to nonresponders. Higher frequencies of effector and memory T cells that expressed multiple inhibitory receptors were seen in SF than in peripheral blood. Notably, inhibitory pathways were operative in blood and synovial T cells from all RA patients, although cells from nonresponder patients were less sensitive to inhibition. Conclusion: Inhibitory receptor expression on T cells from RA patients is inversely correlated with effector T cell function and disease activity and may predict response to treatment. Furthermore, different inhibitory pathways are functional and cooperatively suppress synovial T cells, providing a rationale for new treatment strategies to regulate acute local inflammation.
publishDate 2018
dc.date.none.fl_str_mv 2018-09
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/11336/95902
Onofrio, Luisina Inés; Zacca, Estefanía; Ferrero, Paola Virginia; Acosta, Cristina; Mussano, Eduardo; et al.; Inhibitory Receptor Expression on T Cells as a Marker of Disease Activity and Target to Regulate Effector Cellular Responses in Rheumatoid Arthritis; John Wiley & Sons Inc; Arthritis and Rheumatology; 70; 9; 9-2018; 1429-1439
2326-5205
CONICET Digital
CONICET
url http://hdl.handle.net/11336/95902
identifier_str_mv Onofrio, Luisina Inés; Zacca, Estefanía; Ferrero, Paola Virginia; Acosta, Cristina; Mussano, Eduardo; et al.; Inhibitory Receptor Expression on T Cells as a Marker of Disease Activity and Target to Regulate Effector Cellular Responses in Rheumatoid Arthritis; John Wiley & Sons Inc; Arthritis and Rheumatology; 70; 9; 9-2018; 1429-1439
2326-5205
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1002/art.40521
info:eu-repo/semantics/altIdentifier/url/https://onlinelibrary.wiley.com/doi/full/10.1002/art.40521
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
application/pdf
application/pdf
dc.publisher.none.fl_str_mv John Wiley & Sons Inc
publisher.none.fl_str_mv John Wiley & Sons Inc
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
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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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