title: Role of T cells for cytokine production and outcome in a model of acute septic peritonitis.
abstract: Although it is generally accepted that early defense mechanisms are controlled by cells of the innate immune system, T cells were found to be crucial for host resistance against acute septic peritonitis. However, the mechanisms by which T cells mediate protection are not fully understood. Here, we demonstrate mice deficient for recombinase-activating gene (RAG) 1, which lack mature B and T cells, showed enhanced susceptibility and impaired bacterial clearance in a model of acute septic peritonitis. Whereas B-cell-deficient muMT mice showed no significant difference in the survival rate after peritonitis induction, T-cell-deficient Balb/c nude mice exhibited reduced survival. Importantly, analysis of cytokine production in both RAG-1-deficient and T-cell-deficient nude mice indicated strongly attenuated production of IL-12, interferon (IFN) gamma, and IL-10 during sepsis. Reduced cytokine levels were detected both in serum and in organ extracts of septic mice. Direct analysis of T cells isolated from septic mice demonstrated that T cells respond to an acute septic challenge by increased production of IFN-gamma and IL-10. Moreover, bacterial numbers in spleens of septic RAG-1-deficient mice were significantly increased as compared with controls, suggesting that T cells are engaged in the early antibacterial immune defense during sepsis, possibly via the production of IFN-gamma. In summary, these results imply that T cells contribute to protective immune responses against acute systemic infections via their ability to produce crucial immune mediators.
authors.affiliation: Department of Surgery, Technische Universität München, Ismaninger Strasse 22, 81675 Munich, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Reim
authors.forename: Kay
authors.initials: K
authors.lastname: Westenfelder
authors.forename: Simone
authors.initials: S
authors.lastname: Kaiser-Moore
authors.forename: Sylvia
authors.initials: S
authors.lastname: Schlautkötter
authors.forename: Bernhard
authors.initials: B
authors.lastname: Holzmann
authors.forename: Heike
authors.initials: H
authors.lastname: Weighardt
mesh_terms: D000208:Acute Disease; D000818:Animals; D016207:Cytokines / Q000235:genetics / Q000276:immunology*; D004195:Disease Models, Animal; D018398:Homeodomain Proteins / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010538:Peritonitis / Q000235:genetics / Q000276:immunology* / Q000382:microbiology; D018805:Sepsis / Q000235:genetics / Q000276:immunology* / Q000382:microbiology; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D016207:Cytokines; D018398:Homeodomain Proteins; C064658:RAG-1 protein