Type I IFN-producing CD4 Valpha14i NKT cells facilitate priming of IL-10-producing CD8 T cells by hepatocytes.
Upon entering the liver CD8 T cells encounter large numbers of NKT cells patrolling the hepatocyte (HC) surface facing the perisinusoidal space. We asked whether hepatic NKT cells modulate the priming of CD8 T cells by HC. Hepatic (alpha-galactosyl-ceramide-loaded CD1d dimer binding) NKT cells produce predominantly IL-4 when stimulated with glycolipid-presenting HC but predominantly IFN-gamma when stimulated with glycolipid-presenting dendritic cells. These NKT cells prime naive CD8 T cells to a (K(b)-presented) peptide ligand if they simultaneously recognize a CD1d-binding glycolipid presented to them on the surface of the responding CD8 T cells that they prime. No IL-10-producing CD8 T cells are detected if these T cells are primed by either HC or NKT cells. In contrast, IL-10 is produced by HC-primed CD8 T cells if IFN-beta-producing NKT cells are coactivated by the same HC presenting a glycolipid (in the context of CD1d) and an antigenic peptide (in the context of K(b)). Hence, IL-10-producing CD8 T cells are generated in a type I IFN-dependent manner if the three cell types (CD8 T cells, NKT cells, and ligand-presenting HC) specifically and closely interact. IL-10-producing CD8 T cells generated under these conditions down-modulate IL-2 (and proliferative) responses of naive CD4 or CD8 T cells primed by DC. If in close proximity, NKT cells can thus locally modulate the phenotype of CD8 T cells during their priming by HC thereby limiting the local activation of proinflammatory immune effector cells and protecting the liver against immune injury.
Wahl
Christian
C
Department of Internal Medicine I, University of Ulm, Ulm, Germany.
Bochtler
Petra
P
Schirmbeck
Reinhold
R
Reimann
Jörg
J
D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D018949:Antigens, CD1 / Q000235:genetics / Q000276:immunology; D055610:Antigens, CD1d; D015704:CD4 Antigens / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology; D015536:Down-Regulation / Q000276:immunology; D005699:Galactosylceramides / Q000276:immunology; D022781:Hepatocytes / Q000276:immunology*; D007249:Inflammation / Q000276:immunology; D007370:Interferon Type I / Q000276:immunology*; D016753:Interleukin-10 / Q000276:immunology*; D007376:Interleukin-2 / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology*; D008099:Liver / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D018345:Mice, Knockout; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology*
D018949:Antigens, CD1; D055610:Antigens, CD1d; D015704:CD4 Antigens; D005699:Galactosylceramides; D007370:Interferon Type I; D007376:Interleukin-2; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016753:Interleukin-10