Recently primed CD8+ T cells entering the liver induce hepatocytes to interact with naïve CD8+ T cells in the mouse.
Large number of T cells traffic through the liver. In order to examine the effects of such traffic on the phenotype of hepatocytes, we vaccinated mice using DNA vaccines encoding antigens with MHC class I-binding epitopes. Small numbers of activated CD8(+) T blasts (10(5)-10(6)/liver) changed the surface phenotype and cytokine expression profile of hepatocytes (HCs). HCs upregulate surface expression of major histocompatibility complex (MHC) class I molecules and CD1d but not MHC class II molecules Qa-1, CD80, CD86, CD54, or CD95; in addition, they expressed/secreted interleukin (IL)-10 and IL-4 but not IL-1, IL-6, IL-13, interferon (IFN)-gamma, tumor necrosis factor (TNF), IL-4, or IL-27 (i.e., they acquire the HC* phenotype). HCs* (but not HCs) induced specific activation, proliferation, and IFN-gamma, TNF, and IL-13 release of cocultured naïve CD8(+) T cells. In contrast to the specific activation of naïve CD8(+) T cells by dendritic cells (DCs), specific CD8(+) T cell activation by HC* was not down-modulated by IFN-alphabeta. Only recently activated CD8(+) T blasts (but not recently activated CD4(+) T blasts or activated cells of the innate immune system, including natural killer T [NKT] cells) induced the HC* phenotype that is prominent from day 10 to day 20 postvaccination (i.e., time points at which peak numbers of recently primed CD8(+) T blasts are found in the liver). In conclusion, recently activated CD8(+) T blasts that enter the liver postimmunization in small numbers can transiently modulate the phenotype of HC, allowing them to activate naïve CD8(+) T cells with unrelated specificities.
Dikopoulos
Nektarios
N
Department of Medical Microbiology and Immunology, University of Ulm, Ulm, Germany. nektarios.dikopoulos@medizin.uni-ulm.de
Wegenka
Ursula
U
Kröger
Andrea
A
Hauser
Hansjörg
H
Schirmbeck
Reinhold
R
Reimann
Jörg
J
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology*; D002450:Cell Communication / Q000276:immunology*; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000235:genetics; D022781:Hepatocytes / Q000166:cytology* / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000235:genetics; D000949:Histocompatibility Antigens Class II / Q000235:genetics; D018398:Homeodomain Proteins / Q000235:genetics; D016753:Interleukin-10 / Q000235:genetics; D015847:Interleukin-4 / Q000235:genetics; D007694:Killer Cells, Natural / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010641:Phenotype; D015854:Up-Regulation / Q000276:immunology
D004268:DNA-Binding Proteins; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D018398:Homeodomain Proteins; C499308:Rag2 protein, mouse; C064655:V(D)J recombination activating protein 2; C064658:RAG-1 protein; D016753:Interleukin-10; D015847:Interleukin-4