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Detrimental role for CD4+ T lymphocytes in murine diffuse peritonitis due to inhibition of local bacterial elimination
  1. Mandy Busse (mandyklabunde{at}gmx.de)
  1. Institut für Immunologie und Transfusionsmedizin, Universität Greifswald, Germany, Germany
    1. Tobias Traeger (traeger{at}uni-greifswald.de)
    1. Klinik und Poliklinik für Chirurgie, Universität Greifswald, Germany, Germany
      1. Christian Pötschke (christian_poetschke{at}freenet.de)
      1. Institut für Immunologie und Transfusionsmedizin, Universität Greifswald, Germany, Germany
        1. Anja Billing (anja.billing{at}ins.etat.lu)
        1. Institut für Immunologie und Transfusionsmedizin, Universität Greifswald, Germany, Germany
          1. Annegret Dummer (gleichhinterdersonne{at}gmx.de)
          1. Klinik und Poliklinik für Innere Medizin A, Germany
            1. Erika Friebe (erikafriebe{at}gmx.de)
            1. Institut für Immunologie und Transfusionsmedizin, Universität Greifswald, Germany, Germany
              1. Cornelia Kiank (cornelia.kiank{at}gmx.de)
              1. Institut für Immunologie und Transfusionsmedizin, Universität Greifswald, Germany, Germany
                1. Uwe Grunwald (grunwald{at}uni-greifswald.de)
                1. Institut für Immunologie und Transfusionsmedizin, Universität Greifswald, Germany, Germany
                  1. Robert S. Jack (jack{at}uni-greifswald.de)
                  1. Institut für Immunologie und Transfusionsmedizin, Universität Greifswald, Germany, Germany
                    1. Christine Schütt (schuett{at}uni-greifswald.de)
                    1. Institut für Immunologie und Transfusionsmedizin, Universität Greifswald, Germany, Germany
                      1. Claus-Dieter Heidecke (heidecke{at}uni-greifswald.de)
                      1. Klinik und Poliklinik für Chirurgie, Universität Greifswald, Germany, Germany
                        1. Stefan Maier (maier{at}uni-greifswald.de)
                        1. Klinik und Poliklinik für Chirurgie, Universität Greifswald, Germany, Germany
                          1. Barbara M. Bröker (broeker{at}uni-greifswald.de)
                          1. Institut für Immunologie und Transfusionsmedizin, Universität Greifswald, Germany, Germany

                            Abstract

                            Background: Abdominal sepsis due to intestinal leakage of endogenous gut bacteria is a life threatening condition. In healthy individuals, T lymphocytes have essential functions in balancing the immune response to the commensal gut flora. Aim: We wanted to determine how T lymphocytes shape the process of diffuse faecal peritonitis. Methods: In the colon ascendens stent peritonitis (CASP), a clinically relevant mouse model of diffuse peritonitis, we investigated the kinetics of systemic T cell activation by assessment of activation markers. We then depleted CD4+ T cells with monoclonal antibodies and measured survival, bacterial dissemination and cytokine concentrations. T cell receptor signalling was blocked with tacrolimus. Results: In diffuse peritonitis, CD4+ T cells, both Foxp3- and Foxp3+, became systemically involved within hours and up regulated CTLA-4 and other activation markers. Depletion of the CD4+ T cells enhanced local bacterial clearance from the peritoneal cavity, reduced bacterial dissemination and improved survival. This was accompanied by increased immigration of granulocytes and macrophages into the peritoneum indicating that CD4+ T cells inhibit the local innate immune response. Blockade of T cell receptor (TCR) signalling by tacrolimus did not influence the survival in this peritonitis model, showing that the inhibitory effects of the CD4+ T lymphocytes were independent of TCR-mediated antigen recognition. Conclusion: In diffuse peritonitis caused by commensal gut bacteria the CD4+ T lymphocytes exert a net negative effect on the local anti-bacterial defence and thereby contribute to bacterial dissemination and poor outcome.

                            • T cells
                            • bacterial elimination
                            • peritonitis
                            • rodent

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