Identification of a Kupffer cell subset capable of reverting the T cell dysfunction induced by hepatocellular priming
Giorgia De Simone, Francesco Andreata, Camille Blériot, Valeria Fumagalli, Chiara Laura, José Manuel García-Manteiga, Pietro Di Lucia, Stefano Gilotto, Xenia Ficht, Federico F. De Ponti, Elisa Bono, Leonardo Giustini, Gioia Ambrosi, Marta Mainetti, Paola Zordan, Alexandre P. Bénéchet, Micol Ravà, Svetoslav Chakarov, Federica Moalli, Marc Bajénoff, Luca G. Guidotti, Florent Ginhoux, Matteo Iannacone
Abstract
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.