Dynamics and genomic landscape of CD8+ T cells undergoing hepatic priming.
Nature
; 574(7777): 200-205, 2019 10.
Article
em En
| MEDLINE
| ID: mdl-31582858
ABSTRACT
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Vírus da Hepatite B
/
Linfócitos T CD8-Positivos
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Hepatócitos
/
Apresentação Cruzada
Limite:
Animals
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Female
/
Humans
/
Male
Idioma:
En
Revista:
Nature
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Itália