title: Liver-primed memory T cells generated under noninflammatory conditions provide anti-infectious immunity.
abstract: 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.
authors.affiliation: Institutes of Molecular Medicine and Experimental Immunology, Rheinische Friedrich-Wilhelms-Universität, 53105 Bonn, Germany.
authors.forename: Jan P
authors.initials: JP
authors.lastname: Böttcher
authors.forename: Oliver
authors.initials: O
authors.lastname: Schanz
authors.forename: Dirk
authors.initials: D
authors.lastname: Wohlleber
authors.forename: Zeinab
authors.initials: Z
authors.lastname: Abdullah
authors.forename: Svenja
authors.initials: S
authors.lastname: Debey-Pascher
authors.forename: Andrea
authors.initials: A
authors.lastname: Staratschek-Jox
authors.forename: Bastian
authors.initials: B
authors.lastname: Höchst
authors.forename: Silke
authors.initials: S
authors.lastname: Hegenbarth
authors.forename: Jessica
authors.initials: J
authors.lastname: Grell
authors.forename: Andreas
authors.initials: A
authors.lastname: Limmer
authors.forename: Imke
authors.initials: I
authors.lastname: Atreya
authors.forename: Markus F
authors.initials: MF
authors.lastname: Neurath
authors.forename: Dirk H
authors.initials: DH
authors.lastname: Busch
authors.forename: Edgar
authors.initials: E
authors.lastname: Schmitt
authors.forename: Peter
authors.initials: P
authors.lastname: van Endert
authors.forename: Waldemar
authors.initials: W
authors.lastname: Kolanus
authors.forename: Christian
authors.initials: C
authors.lastname: Kurts
authors.forename: Joachim L
authors.initials: JL
authors.lastname: Schultze
authors.forename: Linda
authors.initials: L
authors.lastname: Diehl
authors.forename: Percy A
authors.initials: PA
authors.lastname: Knolle
mesh_terms: D000818:Animals; D018106:CD28 Antigens / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D045142:Cross-Priming; D003713:Dendritic Cells / Q000276:immunology; D042783:Endothelial Cells / Q000276:immunology; D020869:Gene Expression Profiling; D007113:Immunity, Innate; D007156:Immunologic Memory; D008089:Listeria monocytogenes / Q000276:immunology; D008099:Liver / Q000166:cytology / Q000276:immunology* / Q000382:microbiology; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D039942:Neuropilin-1 / Q000235:genetics / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D053707:Receptors, Interleukin-12 / Q000276:immunology
chemical_list: D018106:CD28 Antigens; D011948:Receptors, Antigen, T-Cell; D053707:Receptors, Interleukin-12; D039942:Neuropilin-1