UCL Discovery
UCL home » Library Services » Electronic resources » UCL Discovery

PD-1 Blockade Modulates Functional Activities of Exhausted-Like T Cell in Patients With Cutaneous Leishmaniasis

de Moura, RG; Covre, LP; Fantecelle, CH; Torres Gajardo, VA; Cunha, CB; Stringari, LL; Belew, AT; ... Oliveira Gomes, DC; + view all (2021) PD-1 Blockade Modulates Functional Activities of Exhausted-Like T Cell in Patients With Cutaneous Leishmaniasis. Frontiers in Immunology , 12 , Article 632667. 10.3389/fimmu.2021.632667. Green open access

[thumbnail of fimmu-12-632667.pdf]
Preview
Text
fimmu-12-632667.pdf - Published Version

Download (9MB) | Preview

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-γ production, but not TNF-α 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.

Type: Article
Title: PD-1 Blockade Modulates Functional Activities of Exhausted-Like T Cell in Patients With Cutaneous Leishmaniasis
Open access status: An open access version is available from UCL Discovery
DOI: 10.3389/fimmu.2021.632667
Publisher version: https://doi.org/10.3389/fimmu.2021.632667
Language: English
Additional information: © 2021 Garcia de Moura, Covre, Fantecelle, Gajardo, Cunha, Stringari, Belew, Daniel, Zeidler, Tadokoro, de Matos Guedes, Zanotti, Mosser, Falqueto, Akbar and Gomes. This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/).
Keywords: cutaneous leishmaniasis, Leishmania braziliensis, T cell exhaustion, PD-1, inhibitory checkpoint receptors, senescent T cells, immunosenescenc
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Experimental and Translational Medicine
URI: https://discovery.ucl.ac.uk/id/eprint/10127917
Downloads since deposit
29Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item