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 μMT 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) γ, 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-γ 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-γ. 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.

ABBREVIATIONS-CASP-colon ascendens stent peritonitis; CLP-cecal ligation and puncture; CXCL1-chemokine (CXC motif) ligand 1; RAG-recombinase-activating gene; SOCS5-suppressor of cytokine signaling-5