biostudies-literatureDe Simone GEuropean Research Council2089-2100.e8https://www.ebi.ac.uk/biostudies/studies/S-EPMC8459394biostudies-literatureUnknown54(9)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 theImmunityIdentification of a Kupffer cell subset capable of reverting the T cell dysfunction induced by hepatocellular priming.PMC8459394957502725038Garcia-Manteiga JMFicht XAndreata FGuidotti LGBleriot CGilotto SMoalli FBono EBChakarov SMainetti MAmbrosi GGiustini LZordan PBenechet APGinhoux FDe Simone GIannacone MLaura CBajenoff MFumagalli VDi Lucia PDe Ponti FFRava MfalseIdentification of a Kupffer cell subset capable of reverting the T cell dysfunction induced by hepatocellular priming.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 the2021-01-01T00:00:00Z2021 Sep2026-06-17T05:14:39.127Z2022-02-11T11:29:29.957ZS-EPMC84593943446977410.1016/j.immuni.2021.05.005