Ito cells are liver-resident antigen-presenting cells for activating T cell responses.
Here we identified Ito cells (hepatic stellate cells, HSC), known for storage of vitamin A and participation in hepatic fibrosis, as professional liver-resident antigen-presenting cells (APC). Ito cells efficiently presented antigens to CD1-, major histocompatibility complex (MHC)-I-, and MHC-II-restricted T cells. Ito cells presented lipid antigens to CD1-restricted T lymphocytes such as natural killer T (NKT) cells and promoted homeostatic proliferation of liver NKT cells through interleukin-15. Moreover, Ito cells presented antigenic peptides to CD8(+) and CD4(+) T cells and mediated crosspriming of CD8(+) T cells. Peptide-specific T cells were activated by transgenic Ito cells presenting endogenous neoantigen. Upon bacterial infection, Ito cells elicited antigen-specific T cells and mediated protection. In contrast to other liver cell types that have been implicated in induction of immunological tolerance, our data identify Ito cells as professional intrahepatic APCs activating T cells and eliciting a multitude of T cell responses specific for protein and lipid antigens.
Winau
Florian
F
Department of Immunology, Max-Planck-Institute for Infection Biology, Schumannstrasse 21-22, 10117 Berlin, Germany. winau@mpiib-berlin.mpg.de
Hegasy
Guido
G
Weiskirchen
Ralf
R
Weber
Stephan
S
Cassan
Cécile
C
Sieling
Peter A
PA
Modlin
Robert L
RL
Liblau
Roland S
RS
Gressner
Axel M
AM
Kaufmann
Stefan H E
SH
D019264:Adoptive Transfer; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D000938:Antigen-Presenting Cells / Q000166:cytology* / Q000276:immunology*; D018949:Antigens, CD1 / Q000378:metabolism; D005434:Flow Cytometry; D019409:Interleukin-15 / Q000378:metabolism; D008088:Listeriosis / Q000276:immunology; D008099:Liver / Q000166:cytology* / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008822:Mice, Transgenic; D018613:Microscopy, Confocal; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology* / Q000821:virology
D018949:Antigens, CD1; D019409:Interleukin-15