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Persistent T cell unresponsiveness associated with chronic visceral leishmaniasis in HIV-coinfected patients

A large proportion of HIV-coinfected visceral leishmaniasis (VL-HIV) patients exhibit chronic disease with frequent VL recurrence. However, knowledge on immunological determinants underlying the disease course is scarce. We longitudinally profiled the circulatory cellular immunity of an Ethiopian HI...

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Main Authors: Vrij, Nicky de (Author) , Pollmann, Julia (Author) , Rezende, Antonio M. (Author) , Ibarra-Meneses, Ana V. (Author) , Pham, Thao-Thy (Author) , Hailemichael, Wasihun (Author) , Kassa, Mekibib (Author) , Bogale, Tadfe (Author) , Melkamu, Roma (Author) , Yeshanew, Arega (Author) , Mohammed, Rezika (Author) , Diro, Ermias (Author) , Maes, Ilse (Author) , Domagalska, Malgorzata A. (Author) , Landuyt, Hanne (Author) , Vogt, Florian (Author) , van Henten, Saskia (Author) , Laukens, Kris (Author) , Cuypers, Bart (Author) , Meysman, Pieter (Author) , Beyene, Hailemariam (Author) , Sisay, Kasaye (Author) , Kibret, Aderajew (Author) , Mersha, Dagnew (Author) , Ritmeijer, Koert (Author) , van Griensven, Johan (Author) , Adriaensen, Wim (Author)
Format: Article (Journal)
Language:English
Published: 3 May 2024
In: Communications biology
Year: 2024, Volume: 7, Pages: 1-13
ISSN:2399-3642
DOI:10.1038/s42003-024-06225-2
Online Access:Verlag, kostenfrei, Volltext: https://doi.org/10.1038/s42003-024-06225-2
Resolving-System, kostenfrei, Volltext: https://www.nature.com/articles/s42003-024-06225-2
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Author Notes:Nicky de Vrij, Julia Pollmann, Antonio M. Rezende, Ana V. Ibarra-Meneses, Thao-Thy Pham, Wasihun Hailemichael, Mekibib Kassa, Tadfe Bogale, Roma Melkamu, Arega Yeshanew, Rezika Mohammed, Ermias Diro, Ilse Maes, Malgorzata A. Domagalska, Hanne Landuyt, Florian Vogt, Saskia van Henten, Kris Laukens, Bart Cuypers, Pieter Meysman, Hailemariam Beyene, Kasaye Sisay, Aderajew Kibret, Dagnew Mersha, Koert Ritmeijer, Johan van Griensven & Wim Adriaensen
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Summary:A large proportion of HIV-coinfected visceral leishmaniasis (VL-HIV) patients exhibit chronic disease with frequent VL recurrence. However, knowledge on immunological determinants underlying the disease course is scarce. We longitudinally profiled the circulatory cellular immunity of an Ethiopian HIV cohort that included VL developers. We show that chronic VL-HIV patients exhibit high and persistent levels of TIGIT and PD-1 on CD8+/CD8- T cells, in addition to a lower frequency of IFN-γ+ TIGIT- CD8+/CD8- T cells, suggestive of impaired T cell functionality. At single T cell transcriptome and clonal resolution, the patients show CD4+ T cell anergy, characterised by a lack of T cell activation and lymphoproliferative response. These findings suggest that PD-1 and TIGIT play a pivotal role in VL-HIV chronicity, and may be further explored for patient risk stratification. Our findings provide a strong rationale for adjunctive immunotherapy for the treatment of chronic VL-HIV patients to break the recurrent disease cycle.
Item Description:Gesehen am 28.03.2025
Physical Description:Online Resource
ISSN:2399-3642
DOI:10.1038/s42003-024-06225-2

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