title: Failure of CD4 T-cells to respond to liver-derived antigen and to provide help to CD8 T-cells.
abstract: CD4 T-cell help is required for the induction of efficient CD8 T-cells responses and the generation of memory cells. Lack of CD4 T-cell help may contribute to an exhausted CD8 phenotype and viral persistence. Little is known about priming of CD4 T-cells by liver-derived antigen. We used TF-OVA mice expressing ovalbumin in hepatocytes to investigate CD4 T-cell priming by liver-derived antigen and the impact of CD4 T-cell help on CD8 T-cell function. Naïve and effector CD4 T-cells specific for ovalbumin were transferred into TF-OVA mice alone or together with naïve ovalbumin-specific CD8 T-cells. T-cell activation and function were analyzed. CD4 T-cells ignored antigen presented by liver antigen-presenting cells (APCs) in vitro and in vivo but were primed in the liver-draining lymph node and the spleen. No priming occurred in the absence of bone-marrow derived APCs capable of presenting ovalbumin in vivo. CD4 T-cells primed in TF-OVA mice displayed defective Th1-effector function and caused no liver damage. CD4 T-cells were not required for the induction of hepatitis by CD8 T-cells. Th1-effector but not naïve CD4 T-cells augmented the severity of liver injury caused by CD8 T-cells. Our data demonstrate that CD4 T-cells fail to respond to liver-derived antigen presented by liver APCs and develop defective effector function after priming in lymph nodes and spleen. The lack of CD4 T-cell help may be responsible for insufficient CD8 T-cell function against hepatic antigens.
authors.affiliation: Department of Hepatology and Gastroenterology, Charité Universitätsmedizin Berlin, Campus Virchow-Klinikum, Berlin, Germany.
authors.forename: Katja
authors.initials: K
authors.lastname: Derkow
authors.forename: Anja
authors.initials: A
authors.lastname: Müller
authors.forename: Ira
authors.initials: I
authors.lastname: Eickmeier
authors.forename: Daniel
authors.initials: D
authors.lastname: Seidel
authors.forename: Marcos Vicinius
authors.initials: MV
authors.lastname: Rust Moreira
authors.forename: Nils
authors.initials: N
authors.lastname: Kruse
authors.forename: Katja
authors.initials: K
authors.lastname: Klugewitz
authors.forename: Justine
authors.initials: J
authors.lastname: Mintern
authors.forename: Bertram
authors.initials: B
authors.lastname: Wiedenmann
authors.forename: Eckart
authors.initials: E
authors.lastname: Schott
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D000941:Antigens / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D005260:Female; D005434:Flow Cytometry; D051379:Mice
chemical_list: D000941:Antigens