Attenuated effector T cells are linked to control of chronic HBV infection

Heim, Kathrin, Saga, Sagar, Sogukpinar, Özlem, Llewellyn-Lacey, Sian, Price, David A. ORCID: https://orcid.org/0000-0001-9416-2737, Emmerich, Florian, Kraft, Anke R. M., Cornberg, Markus, Kielbassa, Sophie, Knolle, Percy, Wohlleber, Dirk, Bengsch, Bertram, Boettler, Tobias, Neumann-Haefelin, Christoph, Thimme, Robert and Hofmann, Maike 2024. Attenuated effector T cells are linked to control of chronic HBV infection. Nature Immunology 25 (9) , pp. 1650-1662. 10.1038/s41590-024-01928-4

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Abstract

Hepatitis B virus (HBV)-specific CD8+ T cells play a dominant role during acute-resolving HBV infection but are functionally impaired during chronic HBV infection in humans. These functional deficits have been linked with metabolic and phenotypic heterogeneity, but it has remained unclear to what extent different subsets of HBV-specific CD8+ T cells still suppress viral replication. We addressed this issue by deep profiling, functional testing and perturbation of HBV-specific CD8+ T cells during different phases of chronic HBV infection. Our data revealed a mechanism of effector CD8+ T cell attenuation that emerges alongside classical CD8+ T cell exhaustion. Attenuated HBV-specific CD8+ T cells were characterized by cytotoxic properties and a dampened effector differentiation program, determined by antigen recognition and TGFβ signaling, and were associated with viral control during chronic HBV infection. These observations identify a distinct subset of CD8+ T cells linked with immune efficacy in the context of a chronic human viral infection with immunotherapeutic potential.

Item Type:	Article
Date Type:	Published Online
Status:	Published
Schools:	Medicine
Additional Information:	License information from Publisher: LICENSE 1: URL: http://creativecommons.org/licenses/by-nc-nd/4.0/, Type: open-access
Publisher:	Nature Research
ISSN:	1529-2908
Date of First Compliant Deposit:	2 September 2024
Date of Acceptance:	12 July 2024
Last Modified:	02 Sep 2024 10:15
URI:	https://orca.cardiff.ac.uk/id/eprint/171711

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