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Identification of a Kupffer cell subset capable of reverting the T cell dysfunction induced by hepatocellular priming

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.
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https://hal-amu.archives-ouvertes.fr/hal-03374472
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Submitted on : Tuesday, October 12, 2021 - 10:34:19 AM
Last modification on : Friday, April 1, 2022 - 3:49:53 AM

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Giorgia de Simone, Francesco Andreata, Camille Bleriot, Valeria Fumagalli, Chiara Laura, et al.. Identification of a Kupffer cell subset capable of reverting the T cell dysfunction induced by hepatocellular priming. Immunity, Elsevier, 2021, 54 (9), pp.2089-2100.e8. ⟨10.1016/j.immuni.2021.05.005⟩. ⟨hal-03374472⟩

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