Liver-Primed Memory T Cells Generated under Noninflammatory Conditions Provide Anti-infectious Immunity

• Main Authors: Jan P. Böttcher, Oliver Schanz, Dirk Wohlleber, Zeinab Abdullah, Svenja Debey-Pascher, Andrea Staratschek-Jox, Bastian Höchst, Silke Hegenbarth, Jessica Grell, Andreas Limmer, Imke Atreya, Markus F. Neurath, Dirk H. Busch, Edgar Schmitt, Peter van Endert, Waldemar Kolanus, Christian Kurts, Joachim L. Schultze, Linda Diehl, Percy A. Knolle
• Format: Article
• Language: English
• Published: Elsevier 2013-03-01
• Series: Cell Reports
• Online Access: http://www.sciencedirect.com/science/article/pii/S2211124713000673

Development of CD8+ T cell (CTL) immunity or tolerance is linked to the conditions during T cell priming. Dendritic cells (DCs) matured during inflammation generate effector/memory T cells, whereas immature DCs cause T cell deletion/anergy. We identify a third outcome of T cell priming in absence of inflammation enabled by cross-presenting liver sinusoidal endothelial cells. Such priming generated memory T cells that were spared from deletion by immature DCs. Similar to central memory T cells, liver-primed T cells differentiated into effector CTLs upon antigen re-encounter on matured DCs even after prolonged absence of antigen. Their reactivation required combinatorial signaling through the TCR, CD28, and IL-12R and controlled bacterial and viral infections. Gene expression profiling identified liver-primed T cells as a distinct Neuropilin-1+ memory population. Generation of liver-primed memory T cells may prevent pathogens that avoid DC maturation by innate immune escape from also escaping adaptive immunity through attrition of the T cell repertoire.