title: Influence of CD8 T cell priming in liver and gut on the enterohepatic circulation.
abstract: OBJECTIVE
  The enterohepatic circuit of T cells may be responsible for the development of autoimmune liver disease. We employed transgenic mice to characterize phenotype and migration patterns of CD8 T cells activated in liver and gut.
  
  
  METHODS
  We studied the migration of antigen-specific CD8 T cells primed in liver or gut after transfer in wild-type mice or mice that express ovalbumin in liver or gut. We performed transcriptome analysis of these two distinct T cell populations and confirmed our findings by flow cytometry.
  
  
  RESULTS
  Specific migration patterns were induced by activation of CD8 T cells in gut or liver. Gut-activated CD8 T cells expressed α4β7 and CCR9 and migrated to the gut and to the liver. Liver-activated T cells expressed integrins α4, α6, β1, α4β7 as well as CD62L, Ly6C, and neuropilin-1 and retained the capability to re-circulate through lymph nodes. Presence of the antigen increased retention of both types of activated T cells in the liver, but migration of liver-activated T cells to the gut was prohibited.
  
  
  CONCLUSIONS
  CD8 T cells primed in the liver in vivo are not capable of migrating to the gut, implying that the enterohepatic circuit of CD8 T cells is in fact a one-way road from the gut to the liver. Priming of CD8 T cells in the liver results in a distinct phenotype with attributes of central memory cells and induces a unique homing pattern. Gut-primed T cells preferentially home to the liver, in principle enabling them to induce autoimmune liver disease.
authors.affiliation: Dept. of Hepatology and Gastroenterology, Charité Universitätsmedizin, CVK, Berlin, Germany.
authors.forename: Ira
authors.initials: I
authors.lastname: Eickmeier
authors.affiliation: Dept. of Hepatology and Gastroenterology, Charité Universitätsmedizin, CVK, Berlin, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Seidel
authors.affiliation: German Rheumatism Research Center, Berlin, Germany.
authors.forename: Joachim R
authors.initials: JR
authors.lastname: Grün
authors.affiliation: Dept. of Neurology, Charité Universitätsmedizin, CCM, Berlin, Germany.
authors.forename: Katja
authors.initials: K
authors.lastname: Derkow
authors.affiliation: Dept. of Neurology, Charité Universitätsmedizin, CCM, Berlin, Germany; Cluster of Excellence NeuroCure, Charité Universitätsmedizin Berlin, Germany.
authors.forename: Seija
authors.initials: S
authors.lastname: Lehnardt
authors.affiliation: Dept. of Gastroenterology, Infectious Diseases and Rheumatology, Charité Universitätsmedizin, CBF, Berlin, Germany.
authors.forename: Anja A
authors.initials: AA
authors.lastname: Kühl
authors.affiliation: Dept. of Rheumatology and Clinical Immunology, Charité Universitätsmedizin, CCM, Berlin, Germany.
authors.forename: Alf
authors.initials: A
authors.lastname: Hamann
authors.affiliation: Dept. of Hepatology and Gastroenterology, Charité Universitätsmedizin, CVK, Berlin, Germany. Electronic address: eckart.schott@charite.de.
authors.forename: Eckart
authors.initials: E
authors.lastname: Schott
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002465:Cell Movement / Q000276:immunology*; D015209:Cholangitis, Sclerosing / Q000235:genetics / Q000276:immunology*; D004195:Disease Models, Animal; D004764:Enterohepatic Circulation / Q000276:immunology*; D019693:Hepatitis, Autoimmune / Q000235:genetics / Q000276:immunology*; D007422:Intestines / Q000276:immunology; D008099:Liver / Q000276:immunology; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000235:genetics / Q000276:immunology; D010641:Phenotype; D059467:Transcriptome / Q000276:immunology
chemical_list: D010047:Ovalbumin
keywords: Autoimmune liver disease; CD8 T cells; Liver immunology; Primary sclerosing cholangitis; T-cell activation; T-cell migration