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
en 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.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Interleucina-2
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Presentación de Antígeno
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Linfocitos T CD8-positivos
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Reactividad Cruzada
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Macrófagos del Hígado
Tipo de estudio:
Diagnostic_studies
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Prognostic_studies
Límite:
Animals
Idioma:
En
Año:
2021
Tipo del documento:
Article