Dynamics and genomic landscape of CD8; +; T cells undergoing hepatic priming

Bénéchet, Alexandre P. and De Simone, Giorgia and Di Lucia, Pietro and Cilenti, Francesco and Barbiera, Giulia and Le Bert, Nina and Fumagalli, Valeria and Lusito, Eleonora and Moalli, Federica and Bianchessi, Valentina and Andreata, Francesco and Zordan, Paola and Bono, Elisa and Giustini, Leonardo and Bonilla, Weldy V. and Bleriot, Camille and Kunasegaran, Kamini and Gonzalez-Aseguinolaza, Gloria and Pinschewer, Daniel D. and Kennedy, Patrick T. F. and Naldini, Luigi and Kuka, Mirela and Ginhoux, Florent and Cantore, Alessio and Bertoletti, Antonio and Ostuni, Renato and Guidotti, Luca G. and Iannacone, Matteo. (2019) Dynamics and genomic landscape of CD8; +; T cells undergoing hepatic priming. Nature, 574 (7777). pp. 200-205.

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Official URL: https://edoc.unibas.ch/75771/

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The responses of CD8; +; T cells to hepatotropic viruses such as hepatitis B range from dysfunction to differentiation into effector cells, but the mechanisms that underlie these distinct outcomes remain poorly understood. Here we show that priming by Kupffer cells, which are not natural targets of hepatitis B, leads to differentiation of CD8; +; T cells into effector cells that form dense, extravascular clusters of immotile cells scattered throughout the liver. By contrast, priming by hepatocytes, which are natural targets of hepatitis B, leads to local activation and proliferation of CD8; +; T cells but not to differentiation into effector cells; these cells form loose, intravascular clusters of motile cells that coalesce around portal tracts. Transcriptomic and chromatin accessibility analyses reveal unique features of these dysfunctional CD8; +; T cells, with limited overlap with those of exhausted or tolerant T cells; accordingly, CD8; +; T cells primed by hepatocytes cannot be rescued by treatment with anti-PD-L1, but instead respond to IL-2. These findings suggest immunotherapeutic strategies against chronic hepatitis B infection.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Division of Medical Microbiology > Experimental Virology (Pinschewer)
UniBasel Contributors:Pinschewer, Daniel
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Nature Research
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:25 May 2020 09:24
Deposited On:30 Mar 2020 11:48

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