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Seminar

Monday, November 25th, 2019
11h30
Centre de Recherche - Paris - Amphithéâtre Constant-Burg - 12 rue Lhomond, Paris 5e

Spatiotemporal dynamics and genomic landscape of CD8+ T cells undergoing intrahepatic priming

CD8+ T cell responses to hepatotropic viruses like HBV range from dysfunction to differentiation into effector cells,
but the mechanisms underlying these distinct outcomes remain poorly understood. Here we show that priming by
Kupffer cells –not natural targets of HBV – leads to differentiation into effector cells that form dense, extravascular
clusters of rather immotile cells scattered throughout the liver. By contrast, priming by hepatocytes – natural targets
of HBV ‐ leads to local activation and proliferation but lack of differentiation into effector cells; these cells form
loose, intravascular clusters of motile cells that coalesce around portal tracts. Transcriptomic and chromatin
accessibility analyses unveil 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 anti‐PD‐L1
treatment, but instead respond to IL‐2. These findings suggest new immunotherapeutic strategies against chronic
HBV infection.

Speaker(s)

Matteo Iannacone

San Raffaele Scientific Institute, Milan, Italy

Invited by

Nicolas Manel
Domain 3 - U932 - Immunity and Cancer

Institut Curie

Ana-Maria Lennon
Domain 3 - U932 - Immunity and Cancer

Institut Curie

Clotilde Théry
Domain 3 - U932 - Immunity and Cancer

Institut Curie

Contact

Elodie Mieville

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Selection of publications

Benechet AP*, De Simone G*, Di Lucia P, Cilenti F, Barbiera G, Le Bert N, Moalli F, Lusito E, Fumagalli V, Bianchessi V, Zordan P, Bono E, Giustini L, Bonilla WD, Bleriot C, Kunasegaran K, Gonzalez-Aseguinolaza G, Pinschewer DD, Kennedy PTF, Naldini L, Kuka M, Ginhoux F, Cantore A, Bertoletti A, Ostuni R#, Guidotti LG#, Iannacone M#✉. Spatiotemporal dynamics and genomic landscape of CD8+ T cells undergoing hepatic priming. Nature, in press (*co-first authors; #co-last authors)

Medaglia C*, Giladi A*, Stoler Barak L*, De Giovanni M*, Meir Salame T, Biram A, David E, Iannacone M#✉, Shulman Z#✉, Amit I#✉ (2017) Spatial reconstruction of immune niches by combining photoactivatable fluorescent reporters and single-cell RNA-seq. Science, 358:1622 (*co-first authors; #co-last and co-corresponding authors)

Sammicheli S*, Kuka M*, Di Lucia P, Jimenez de Oya N, De Giovanni M, Fioravanti J, Cristofani C, Maganuco CG, Fallet B, Ganzer L, Sironi L, Mainetti M, Ostuni R, Larimore K, Greenberg PD, de la Torre JC, Guidotti LG, Iannacone M✉ (2016) Inflammatory monocytes hinder antiviral B cell responses. Science Immunology, 1:eaah6789 (*co-first authors)

Guidotti LG*, Inverso D*, Sironi L, Di Lucia P, Fioravanti J, Fiocchi A, Vacca M, Aiolfi R, Sammicheli S, Mainetti M, Ganzer L, Cataudella T, Raimondi A, Gonzalez-Aseguinolaza G, Protzer U, Ruggeri ZM, Chisari FV, Isogawa M, Sitia G, Iannacone M✉ (2015) Immunosurveillance of the liver by intravascular effector CD8+ T cells. Cell, 161:486 (*co-first authors)

Iannacone M*✉, Moseman EA*, Tonti E, Bosurgi L, Henrickson SE, Whelan S, Guidotti LG, von Andrian UH (2010) Subcapsular sinus macrophages prevent CNS invasion on peripheral infection with a neurotropic virus. Nature, 465:1079 (*co-first authors)