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Dynamics and genomic landscape of CD8+ T cells undergoing hepatic priming
by
Moalli, Federica
, Naldini, Luigi
, Bonilla, Weldy V.
, Cilenti, Francesco
, Giustini, Leonardo
, Lusito, Eleonora
, Kunasegaran, Kamini
, Bleriot, Camille
, Ginhoux, Florent
, Le Bert, Nina
, Iannacone, Matteo
, Zordan, Paola
, Kennedy, Patrick T. F.
, Gonzalez-Aseguinolaza, Gloria
, Ostuni, Renato
, Guidotti, Luca G.
, Bono, Elisa
, Bénéchet, Alexandre P.
, Cantore, Alessio
, Di Lucia, Pietro
, De Simone, Giorgia
, Bertoletti, Antonio
, Bianchessi, Valentina
, Kuka, Mirela
, Pinschewer, Daniel D.
, Barbiera, Giulia
, Andreata, Francesco
, Fumagalli, Valeria
in
13/31
/ 13/51
/ 14/19
/ 14/69
/ 38
/ 38/91
/ 45/91
/ 631/250/1619/554/1834/1269
/ 631/250/2152/1566/1618
/ 631/250/251/1567
/ 631/250/255/234/2513/1549
/ 64/60
/ 692/699/1503/234/2513/1549
/ Animals
/ Antigens
/ B7-H1 Antigen - antagonists & inhibitors
/ Bioinformatics
/ CD8 antigen
/ CD8-Positive T-Lymphocytes - cytology
/ CD8-Positive T-Lymphocytes - immunology
/ CD8-Positive T-Lymphocytes - metabolism
/ Cell activation
/ Cell Differentiation
/ Cell proliferation
/ Chromatin
/ Chromatin - metabolism
/ Chronic infection
/ Clusters
/ Coalescing
/ Cross-Priming - immunology
/ Dendritic cells
/ Effector cells
/ Female
/ Gene expression
/ Genomes
/ Hepatitis
/ Hepatitis B
/ Hepatitis B - drug therapy
/ Hepatitis B - immunology
/ Hepatitis B - virology
/ Hepatitis B virus - immunology
/ Hepatocytes
/ Hepatocytes - immunology
/ Hepatocytes - virology
/ Humanities and Social Sciences
/ Humans
/ Immune Tolerance
/ Infections
/ Interleukin 2
/ Interleukin-2 - immunology
/ Interleukin-2 - therapeutic use
/ Kupffer cells
/ Kupffer Cells - immunology
/ Liver
/ Lymphatic system
/ Lymphocyte Activation
/ Lymphocytes
/ Lymphocytes T
/ Male
/ Methods
/ Mice
/ multidisciplinary
/ PD-L1 protein
/ Priming
/ Proteins
/ Science
/ Science (multidisciplinary)
/ T cell receptors
/ Transcriptome - genetics
/ Viruses
2019
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Dynamics and genomic landscape of CD8+ T cells undergoing hepatic priming
by
Moalli, Federica
, Naldini, Luigi
, Bonilla, Weldy V.
, Cilenti, Francesco
, Giustini, Leonardo
, Lusito, Eleonora
, Kunasegaran, Kamini
, Bleriot, Camille
, Ginhoux, Florent
, Le Bert, Nina
, Iannacone, Matteo
, Zordan, Paola
, Kennedy, Patrick T. F.
, Gonzalez-Aseguinolaza, Gloria
, Ostuni, Renato
, Guidotti, Luca G.
, Bono, Elisa
, Bénéchet, Alexandre P.
, Cantore, Alessio
, Di Lucia, Pietro
, De Simone, Giorgia
, Bertoletti, Antonio
, Bianchessi, Valentina
, Kuka, Mirela
, Pinschewer, Daniel D.
, Barbiera, Giulia
, Andreata, Francesco
, Fumagalli, Valeria
in
13/31
/ 13/51
/ 14/19
/ 14/69
/ 38
/ 38/91
/ 45/91
/ 631/250/1619/554/1834/1269
/ 631/250/2152/1566/1618
/ 631/250/251/1567
/ 631/250/255/234/2513/1549
/ 64/60
/ 692/699/1503/234/2513/1549
/ Animals
/ Antigens
/ B7-H1 Antigen - antagonists & inhibitors
/ Bioinformatics
/ CD8 antigen
/ CD8-Positive T-Lymphocytes - cytology
/ CD8-Positive T-Lymphocytes - immunology
/ CD8-Positive T-Lymphocytes - metabolism
/ Cell activation
/ Cell Differentiation
/ Cell proliferation
/ Chromatin
/ Chromatin - metabolism
/ Chronic infection
/ Clusters
/ Coalescing
/ Cross-Priming - immunology
/ Dendritic cells
/ Effector cells
/ Female
/ Gene expression
/ Genomes
/ Hepatitis
/ Hepatitis B
/ Hepatitis B - drug therapy
/ Hepatitis B - immunology
/ Hepatitis B - virology
/ Hepatitis B virus - immunology
/ Hepatocytes
/ Hepatocytes - immunology
/ Hepatocytes - virology
/ Humanities and Social Sciences
/ Humans
/ Immune Tolerance
/ Infections
/ Interleukin 2
/ Interleukin-2 - immunology
/ Interleukin-2 - therapeutic use
/ Kupffer cells
/ Kupffer Cells - immunology
/ Liver
/ Lymphatic system
/ Lymphocyte Activation
/ Lymphocytes
/ Lymphocytes T
/ Male
/ Methods
/ Mice
/ multidisciplinary
/ PD-L1 protein
/ Priming
/ Proteins
/ Science
/ Science (multidisciplinary)
/ T cell receptors
/ Transcriptome - genetics
/ Viruses
2019
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Dynamics and genomic landscape of CD8+ T cells undergoing hepatic priming
by
Moalli, Federica
, Naldini, Luigi
, Bonilla, Weldy V.
, Cilenti, Francesco
, Giustini, Leonardo
, Lusito, Eleonora
, Kunasegaran, Kamini
, Bleriot, Camille
, Ginhoux, Florent
, Le Bert, Nina
, Iannacone, Matteo
, Zordan, Paola
, Kennedy, Patrick T. F.
, Gonzalez-Aseguinolaza, Gloria
, Ostuni, Renato
, Guidotti, Luca G.
, Bono, Elisa
, Bénéchet, Alexandre P.
, Cantore, Alessio
, Di Lucia, Pietro
, De Simone, Giorgia
, Bertoletti, Antonio
, Bianchessi, Valentina
, Kuka, Mirela
, Pinschewer, Daniel D.
, Barbiera, Giulia
, Andreata, Francesco
, Fumagalli, Valeria
in
13/31
/ 13/51
/ 14/19
/ 14/69
/ 38
/ 38/91
/ 45/91
/ 631/250/1619/554/1834/1269
/ 631/250/2152/1566/1618
/ 631/250/251/1567
/ 631/250/255/234/2513/1549
/ 64/60
/ 692/699/1503/234/2513/1549
/ Animals
/ Antigens
/ B7-H1 Antigen - antagonists & inhibitors
/ Bioinformatics
/ CD8 antigen
/ CD8-Positive T-Lymphocytes - cytology
/ CD8-Positive T-Lymphocytes - immunology
/ CD8-Positive T-Lymphocytes - metabolism
/ Cell activation
/ Cell Differentiation
/ Cell proliferation
/ Chromatin
/ Chromatin - metabolism
/ Chronic infection
/ Clusters
/ Coalescing
/ Cross-Priming - immunology
/ Dendritic cells
/ Effector cells
/ Female
/ Gene expression
/ Genomes
/ Hepatitis
/ Hepatitis B
/ Hepatitis B - drug therapy
/ Hepatitis B - immunology
/ Hepatitis B - virology
/ Hepatitis B virus - immunology
/ Hepatocytes
/ Hepatocytes - immunology
/ Hepatocytes - virology
/ Humanities and Social Sciences
/ Humans
/ Immune Tolerance
/ Infections
/ Interleukin 2
/ Interleukin-2 - immunology
/ Interleukin-2 - therapeutic use
/ Kupffer cells
/ Kupffer Cells - immunology
/ Liver
/ Lymphatic system
/ Lymphocyte Activation
/ Lymphocytes
/ Lymphocytes T
/ Male
/ Methods
/ Mice
/ multidisciplinary
/ PD-L1 protein
/ Priming
/ Proteins
/ Science
/ Science (multidisciplinary)
/ T cell receptors
/ Transcriptome - genetics
/ Viruses
2019
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Dynamics and genomic landscape of CD8+ T cells undergoing hepatic priming
Journal Article
Dynamics and genomic landscape of CD8+ T cells undergoing hepatic priming
2019
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Overview
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.
CD8
+
T cells that are primed by hepatocytes differentiate into dysfunctional T cells, which can be rescued by treatment with IL-2.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ 13/51
/ 14/19
/ 14/69
/ 38
/ 38/91
/ 45/91
/ 64/60
/ Animals
/ Antigens
/ B7-H1 Antigen - antagonists & inhibitors
/ CD8-Positive T-Lymphocytes - cytology
/ CD8-Positive T-Lymphocytes - immunology
/ CD8-Positive T-Lymphocytes - metabolism
/ Clusters
/ Female
/ Genomes
/ Hepatitis B virus - immunology
/ Humanities and Social Sciences
/ Humans
/ Interleukin-2 - therapeutic use
/ Liver
/ Male
/ Methods
/ Mice
/ Priming
/ Proteins
/ Science
/ Viruses
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