title: Diet induced obesity has an influence on intrahepatic T cell responses.
abstract: Obesity is accompanied with systemic inflammation and pre-conditions to severe alterations in liver environment and functions. So far, it remains elusive to which extent obesity modulates immune responses during hepatotropic virus infections as well as in autoimmune hepatitis. In this study we investigated the influence of obesity on the intrahepatic immune response, in particular on the function of CD8 T cells as the crucial players in clearance of virus infected hepatocytes.
  
  
  
  We established high fat induced obesity in transgenic mouse models with hepatocyte specific expression of a model antigen (Ova). We investigated the immune response upon adoptive transfer of antigen specific T cells and in mice with continuous thymic output of antigen specific T cells, mimicking the situations upon acute infection and autoimmunity, respectively.
  
  
  
  Irrespective of the metabolic condition, adoptive T cell transfer resulted in a transient hepatitis with no obvious differences concerning the acute T cell response. In the situation of autoimmunity, we observed a transient hepatitis in lean mice, whereas an extended hepatitis with a reduced antigen clearance capacity was found in obese mice.
  
  
  
  Our results demonstrate that obesity affects T cell function and increases the severity of autoimmune hepatitis while it has no impact on the acute T cell response.
authors.affiliation: Model Systems for Infection and Immunity, Helmholtz Centre for Infection Research, Inhoffenstr. 7, 38124 Braunschweig, Germany.
authors.forename: Pratibha
authors.initials: P
authors.lastname: Gaur
authors.affiliation: Model Systems for Infection and Immunity, Helmholtz Centre for Infection Research, Inhoffenstr. 7, 38124 Braunschweig, Germany.
authors.forename: Marcin
authors.initials: M
authors.lastname: Cebula
authors.affiliation: Model Systems for Infection and Immunity, Helmholtz Centre for Infection Research, Inhoffenstr. 7, 38124 Braunschweig, Germany.
authors.forename: Mathias
authors.initials: M
authors.lastname: Riehn
authors.affiliation: Model Systems for Infection and Immunity, Helmholtz Centre for Infection Research, Inhoffenstr. 7, 38124 Braunschweig, Germany.
authors.forename: Upneet
authors.initials: U
authors.lastname: Hillebrand
authors.affiliation: Model Systems for Infection and Immunity, Helmholtz Centre for Infection Research, Inhoffenstr. 7, 38124 Braunschweig, Germany.
authors.forename: Hansjörg
authors.initials: H
authors.lastname: Hauser
authors.affiliation: Model Systems for Infection and Immunity, Helmholtz Centre for Infection Research, Inhoffenstr. 7, 38124 Braunschweig, Germany; Institute for Experimental Hematology, Hannover Medical School, Carl-Neuberg-Straße 1, 30625 Hannover, Germany. Electronic address: Dagmar.Wirth@helmholtz-hzi.de.
authors.forename: Dagmar
authors.initials: D
authors.lastname: Wirth
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D015551:Autoimmunity / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D004032:Diet; D059305:Diet, High-Fat; D022781:Hepatocytes / Q000276:immunology* / Q000473:pathology; D008099:Liver / Q000276:immunology* / Q000473:pathology; D008111:Liver Function Tests; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D008822:Mice, Transgenic; D009765:Obesity / Q000276:immunology* / Q000473:pathology; D010047:Ovalbumin / Q000276:immunology; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology
chemical_list: D010047:Ovalbumin
keywords: Intrahepatic CD8+ T cell response; Liver infection; Obesity