Identification of a Kupffer cell subset capable of reverting the T cell dysfunction induced by hepatocellular priming.
Immunity
; 54(9): 2089-2100.e8, 2021 09 14.
Article
em En
| MEDLINE
| ID: mdl-34469774
ABSTRACT
Kupffer cells (KCs) are highly abundant, intravascular, liver-resident macrophages known for their scavenger and phagocytic functions. KCs can also present antigens to CD8+ T cells and promote either tolerance or effector differentiation, but the mechanisms underlying these discrepant outcomes are poorly understood. Here, we used a mouse model of hepatitis B virus (HBV) infection, in which HBV-specific naive CD8+ T cells recognizing hepatocellular antigens are driven into a state of immune dysfunction, to identify a subset of KCs (referred to as KC2) that cross-presents hepatocellular antigens upon interleukin-2 (IL-2) administration, thus improving the antiviral function of T cells. Removing MHC-I from all KCs, including KC2, or selectively depleting KC2 impaired the capacity of IL-2 to revert the T cell dysfunction induced by intrahepatic priming. In summary, by sensing IL-2 and cross-presenting hepatocellular antigens, KC2 overcome the tolerogenic potential of the hepatic microenvironment, suggesting new strategies for boosting hepatic T cell immunity.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Interleucina-2
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Apresentação de Antígeno
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Linfócitos T CD8-Positivos
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Apresentação Cruzada
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Células de Kupffer
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Itália