PD-1 Blockade Modulates Functional Activities of Exhausted-Like T Cell in Patients With Cutaneous Leishmaniasis
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2021 |
| Outros Autores: | , , , , , , , , , , , , , , |
| Tipo de documento: | Artigo |
| Idioma: | eng |
| Título da fonte: | Repositório Institucional da FIOCRUZ (ARCA) |
| Texto Completo: | https://www.arca.fiocruz.br/handle/icict/50263 |
Resumo: | Universidade Federal do Espírito Santo. Núcleo de Doenças Infecciosas. Vitória, ES, Brasil. |
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Moura, Renan Garcia deCovre, Luciana PolacoFantecelle, Carlos HenriqueGajardo, Vitor Alejandro TorresCunha, Carla BaroniStringari, Lorenzzo LyrioBelew, Ashton TreyDaniel, Camila BatistaVon Zeidler, Sandra VentorinTadokoro, Carlos EduardoGuedes, Herbert Leonel de MatosZanotti, Raphael LubianaMosser, DavidFalqueto, AloisioAkbar, Arne N.Gomes, Daniel Claudio Oliveira2021-12-09T20:38:09Z2021-12-09T20:38:09Z2021MOURA, Renan Garcia de et al. PD-1 Blockade Modulates Functional Activities of Exhausted-Like T Cell in Patients With Cutaneous Leishmaniasis. Frontiers in Immunology, v. 12, Article 632667, p. 1 - 12, Mar. 2021.1664-3224https://www.arca.fiocruz.br/handle/icict/5026310.3389/fimmu.2021.632667engFrontiers MediaLeishmaniose cutâneaLeishmania braziliensisExaustão de células TCélulas T senescentesReceptores de checkpoint inibitórioCélulas T senescentesImunosenescênciaCutaneous leishmaniasisLeishmania braziliensisT cell exhaustionPD-1Inhibitory checkpoint receptorsSenescent T cellsImmunosenescencePD-1 Blockade Modulates Functional Activities of Exhausted-Like T Cell in Patients With Cutaneous Leishmaniasisinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleUniversidade Federal do Espírito Santo. Núcleo de Doenças Infecciosas. Vitória, ES, Brasil.Universidade Federal do Espírito Santo. Núcleo de Doenças Infecciosas. Vitória, ES, Brasil / Division of Medicine, University College London. London, United Kingdom.Universidade Federal do Espírito Santo. Núcleo de Doenças Infecciosas. Vitória, ES, Brasil.Universidade Federal do Espírito Santo. Núcleo de Doenças Infecciosas. Vitória, ES, Brasil.Universidade Federal do Espírito Santo. Núcleo de Doenças Infecciosas. Vitória, ES, Brasil.Universidade Federal do Espírito Santo. Núcleo de Doenças Infecciosas. Vitória, ES, Brasil.Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, MD, USA / Center for Bioinformatics and Computational Biology, University of Maryland, College Park, MD, United States.Universidade Federal do Espírito Santo. Núcleo de Biotecnologia. Vitória, ES, Brasil.Universidade Federal do Espírito Santo. Núcleo de Biotecnologia. Vitória, ES, Brasil.Universidade Vila Velha. Vila Velha, ES, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Rio de Janeiro, RJ, Brasil / Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Rio de Janeiro, RJ. Brasil.Secretaria Estadual de Saúde do Espírito Santo-SESA. Vitoria, ES, Brasil.Department of Cell Biology and Molecular Genetics, University of Maryland, College Park. MD, United States.Universidade Federal do Espírito Santo. Departamento de Medicina Social. Vitoria, ES, Brasil.Division of Medicine, University College London. London, United Kingdom.Universidade Federal do Espírito Santo. Núcleo de Doenças Infecciosas. Vitória, ES, Brasil / Universidade Federal do Espírito Santo. Núcleo de Biotecnologia. Vitória, ES, Brasil.Patients infected by Leishmania braziliensis develop debilitating skin lesions. The role of inhibitory checkpoint receptors (ICRs) that induce T cell exhaustion during this disease is not known. Transcriptional profiling identified increased expression of ICRs including PD-1, PDL- 1, PDL-2, TIM-3, and CTLA-4 in skin lesions of patients that was confirmed by immunohistology where there was increased expression of PD-1, TIM-3, and CTLA-4 in both CD4+ and CD8+ T cell subsets. Moreover, PDL-1/PDL-2 ligands were increased on skin macrophages compared to healthy controls. The proportions PD1+, but not TIM-3 or CTLA-4 expressing T cells in the circulation were positively correlated with those in the lesions of the same patients, suggesting that PD-1 may regulate T cell function equally in both compartments. Blocking PD-1 signaling in circulating T cells enhanced their proliferative capacity and IFN-g production, but not TNF-a secretion in response to L. braziliensis recall antigen challenge in vitro. While we previously showed a significant correlation between the accumulation of senescent CD8+CD45RA+CD27- T cells in the circulation and skin lesion size in the patients, there was no such correlation between the extent of PD-1 expression by circulating on T cells and the magnitude of skin lesions suggesting that exhausted-like T cells may not contribute to the cutaneous immunopathology. Nevertheless, we identified exhausted-like T cells in both skin lesions and in the blood. Targeting this population by PD-1 blockade may improve T cell function and thus accelerate parasite clearance that would reduce the cutaneous pathology in cutaneous leishmaniasis.info:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-82991https://www.arca.fiocruz.br/bitstream/icict/50263/1/license.txt5a560609d32a3863062d77ff32785d58MD51ORIGINALHerbertGuedes_RenanMoura_etal_IOC_2021.pdfHerbertGuedes_RenanMoura_etal_IOC_2021.pdfapplication/pdf9987004https://www.arca.fiocruz.br/bitstream/icict/50263/2/HerbertGuedes_RenanMoura_etal_IOC_2021.pdf9e5a99e913130019082ff6c2a36bec8fMD52icict/502632021-12-09 17:38:09.526oai:www.arca.fiocruz.br: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ório InstitucionalPUBhttps://www.arca.fiocruz.br/oai/requestrepositorio.arca@fiocruz.bropendoar:21352021-12-09T20:38:09Repositório Institucional da FIOCRUZ (ARCA) - Fundação Oswaldo Cruz (FIOCRUZ)false |
| dc.title.pt_BR.fl_str_mv |
PD-1 Blockade Modulates Functional Activities of Exhausted-Like T Cell in Patients With Cutaneous Leishmaniasis |
| title |
PD-1 Blockade Modulates Functional Activities of Exhausted-Like T Cell in Patients With Cutaneous Leishmaniasis |
| spellingShingle |
PD-1 Blockade Modulates Functional Activities of Exhausted-Like T Cell in Patients With Cutaneous Leishmaniasis Moura, Renan Garcia de Leishmaniose cutânea Leishmania braziliensis Exaustão de células T Células T senescentes Receptores de checkpoint inibitório Células T senescentes Imunosenescência Cutaneous leishmaniasis Leishmania braziliensis T cell exhaustion PD-1 Inhibitory checkpoint receptors Senescent T cells Immunosenescence |
| title_short |
PD-1 Blockade Modulates Functional Activities of Exhausted-Like T Cell in Patients With Cutaneous Leishmaniasis |
| title_full |
PD-1 Blockade Modulates Functional Activities of Exhausted-Like T Cell in Patients With Cutaneous Leishmaniasis |
| title_fullStr |
PD-1 Blockade Modulates Functional Activities of Exhausted-Like T Cell in Patients With Cutaneous Leishmaniasis |
| title_full_unstemmed |
PD-1 Blockade Modulates Functional Activities of Exhausted-Like T Cell in Patients With Cutaneous Leishmaniasis |
| title_sort |
PD-1 Blockade Modulates Functional Activities of Exhausted-Like T Cell in Patients With Cutaneous Leishmaniasis |
| author |
Moura, Renan Garcia de |
| author_facet |
Moura, Renan Garcia de Covre, Luciana Polaco Fantecelle, Carlos Henrique Gajardo, Vitor Alejandro Torres Cunha, Carla Baroni Stringari, Lorenzzo Lyrio Belew, Ashton Trey Daniel, Camila Batista Von Zeidler, Sandra Ventorin Tadokoro, Carlos Eduardo Guedes, Herbert Leonel de Matos Zanotti, Raphael Lubiana Mosser, David Falqueto, Aloisio Akbar, Arne N. Gomes, Daniel Claudio Oliveira |
| author_role |
author |
| author2 |
Covre, Luciana Polaco Fantecelle, Carlos Henrique Gajardo, Vitor Alejandro Torres Cunha, Carla Baroni Stringari, Lorenzzo Lyrio Belew, Ashton Trey Daniel, Camila Batista Von Zeidler, Sandra Ventorin Tadokoro, Carlos Eduardo Guedes, Herbert Leonel de Matos Zanotti, Raphael Lubiana Mosser, David Falqueto, Aloisio Akbar, Arne N. Gomes, Daniel Claudio Oliveira |
| author2_role |
author author author author author author author author author author author author author author author |
| dc.contributor.author.fl_str_mv |
Moura, Renan Garcia de Covre, Luciana Polaco Fantecelle, Carlos Henrique Gajardo, Vitor Alejandro Torres Cunha, Carla Baroni Stringari, Lorenzzo Lyrio Belew, Ashton Trey Daniel, Camila Batista Von Zeidler, Sandra Ventorin Tadokoro, Carlos Eduardo Guedes, Herbert Leonel de Matos Zanotti, Raphael Lubiana Mosser, David Falqueto, Aloisio Akbar, Arne N. Gomes, Daniel Claudio Oliveira |
| dc.subject.other.pt_BR.fl_str_mv |
Leishmaniose cutânea Leishmania braziliensis Exaustão de células T Células T senescentes Receptores de checkpoint inibitório Células T senescentes Imunosenescência |
| topic |
Leishmaniose cutânea Leishmania braziliensis Exaustão de células T Células T senescentes Receptores de checkpoint inibitório Células T senescentes Imunosenescência Cutaneous leishmaniasis Leishmania braziliensis T cell exhaustion PD-1 Inhibitory checkpoint receptors Senescent T cells Immunosenescence |
| dc.subject.en.pt_BR.fl_str_mv |
Cutaneous leishmaniasis Leishmania braziliensis T cell exhaustion PD-1 Inhibitory checkpoint receptors Senescent T cells Immunosenescence |
| description |
Universidade Federal do Espírito Santo. Núcleo de Doenças Infecciosas. Vitória, ES, Brasil. |
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2021 |
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2021-12-09T20:38:09Z |
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2021-12-09T20:38:09Z |
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2021 |
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info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/article |
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MOURA, Renan Garcia de et al. PD-1 Blockade Modulates Functional Activities of Exhausted-Like T Cell in Patients With Cutaneous Leishmaniasis. Frontiers in Immunology, v. 12, Article 632667, p. 1 - 12, Mar. 2021. |
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1664-3224 |
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10.3389/fimmu.2021.632667 |
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MOURA, Renan Garcia de et al. PD-1 Blockade Modulates Functional Activities of Exhausted-Like T Cell in Patients With Cutaneous Leishmaniasis. Frontiers in Immunology, v. 12, Article 632667, p. 1 - 12, Mar. 2021. 1664-3224 10.3389/fimmu.2021.632667 |
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