| Author | Moura, Renan Garcia de | |
| Author | Covre, Luciana Polaco | |
| Author | Fantecelle, Carlos Henrique | |
| Author | Gajardo, Vitor Alejandro Torres | |
| Author | Cunha, Carla Baroni | |
| Author | Stringari, Lorenzzo Lyrio | |
| Author | Belew, Ashton Trey | |
| Author | Daniel, Camila Batista | |
| Author | Von Zeidler, Sandra Ventorin | |
| Author | Tadokoro, Carlos Eduardo | |
| Author | Guedes, Herbert Leonel de Matos | |
| Author | Zanotti, Raphael Lubiana | |
| Author | Mosser, David | |
| Author | Falqueto, Aloisio | |
| Author | Akbar, Arne N. | |
| Author | Gomes, Daniel Claudio Oliveira | |
| Access date | 2021-12-09T20:38:09Z | |
| Available date | 2021-12-09T20:38:09Z | |
| Document date | 2021 | |
| Citation | 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. | pt_BR |
| ISSN | 1664-3224 | pt_BR |
| URI | https://www.arca.fiocruz.br/handle/icict/50263 | |
| Language | eng | pt_BR |
| Publisher | Frontiers Media | pt_BR |
| Rights | open access | |
| Subject in Portuguese | Leishmaniose cutânea | pt_BR |
| Subject in Portuguese | Leishmania braziliensis | pt_BR |
| Subject in Portuguese | Exaustão de células T | pt_BR |
| Subject in Portuguese | Células T senescentes | pt_BR |
| Subject in Portuguese | Receptores de checkpoint inibitório | pt_BR |
| Subject in Portuguese | Células T senescentes | pt_BR |
| Subject in Portuguese | Imunosenescência | pt_BR |
| Title | PD-1 Blockade Modulates Functional Activities of Exhausted-Like T Cell in Patients With Cutaneous Leishmaniasis | pt_BR |
| Type | Article | |
| DOI | 10.3389/fimmu.2021.632667 | |
| Abstract | 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. | pt_BR |
| Affilliation | Universidade Federal do Espírito Santo. Núcleo de Doenças Infecciosas. Vitória, ES, Brasil. | pt_BR |
| Affilliation | Universidade Federal do Espírito Santo. Núcleo de Doenças Infecciosas. Vitória, ES, Brasil / Division of Medicine, University College London. London, United Kingdom. | pt_BR |
| Affilliation | Universidade Federal do Espírito Santo. Núcleo de Doenças Infecciosas. Vitória, ES, Brasil. | pt_BR |
| Affilliation | Universidade Federal do Espírito Santo. Núcleo de Doenças Infecciosas. Vitória, ES, Brasil. | pt_BR |
| Affilliation | Universidade Federal do Espírito Santo. Núcleo de Doenças Infecciosas. Vitória, ES, Brasil. | pt_BR |
| Affilliation | Universidade Federal do Espírito Santo. Núcleo de Doenças Infecciosas. Vitória, ES, Brasil. | pt_BR |
| Affilliation | 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. | pt_BR |
| Affilliation | Universidade Federal do Espírito Santo. Núcleo de Biotecnologia. Vitória, ES, Brasil. | pt_BR |
| Affilliation | Universidade Federal do Espírito Santo. Núcleo de Biotecnologia. Vitória, ES, Brasil. | pt_BR |
| Affilliation | Universidade Vila Velha. Vila Velha, ES, Brasil. | pt_BR |
| Affilliation | 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. | pt_BR |
| Affilliation | Secretaria Estadual de Saúde do Espírito Santo-SESA. Vitoria, ES, Brasil. | pt_BR |
| Affilliation | Department of Cell Biology and Molecular Genetics, University of Maryland, College Park. MD, United States. | pt_BR |
| Affilliation | Universidade Federal do Espírito Santo. Departamento de Medicina Social. Vitoria, ES, Brasil. | pt_BR |
| Affilliation | Division of Medicine, University College London. London, United Kingdom. | pt_BR |
| Affilliation | Universidade Federal do Espírito Santo. Núcleo de Doenças Infecciosas. Vitória, ES, Brasil / Universidade Federal do Espírito Santo. Núcleo de Biotecnologia. Vitória, ES, Brasil. | pt_BR |
| Subject | Cutaneous leishmaniasis | pt_BR |
| Subject | Leishmania braziliensis | pt_BR |
| Subject | T cell exhaustion | pt_BR |
| Subject | PD-1 | pt_BR |
| Subject | Inhibitory checkpoint receptors | pt_BR |
| Subject | Senescent T cells | pt_BR |
| Subject | Immunosenescence | pt_BR |
