Mice depleted of αβ but not γδ T cells are resistant to mortality caused by cecal ligation and puncture

The present study was undertaken to determine whether the mice depleted of alpha beta or gamma delta T cells show resistance to acute polymicrobial sepsis caused by cecal ligation and puncture (CLIP). T-cell receptor beta knockout (beta TCRKO) and T-cell receptor delta knockout (delta TCRKO) mice were used. An additional group of mice was treated with an antibody against the alpha beta T-cell receptor to induce alpha beta T-cell depletion; a subset of alpha beta T cell-deficient mice was also treated with anti-asialoGM1 to deplete natural killer (NK) cells. The mice underwent CILP and were monitored for survival, temperature, acid-base balance, bacterial counts, and cytokine production. The beta TCRKO mice and the wild-type mice treated with anti-P T-cell receptor (anti-TCR beta) antibody showed improved survival after CLP compared with wild-type mice. The treatment of alpha beta T cell-deficient mice with anti-asialoGM1 further improved survival after CLP, especially when the mice were treated with imipenem. The improved survival observed in alpha beta T cell-deficient mice was associated with less hypothermia, improved acid-base balance, and decreased production of the proinflammatory cytokines interleukin (IL) 6 and macrophage inflammatory protein (MIP) 2. Compared with wild-type controls, the overall survival was not improved in delta TCRKO mice. The concentrations of IL-6 and MIP-2 in plasma and cytokine mRNA expression in tissues were not significantly different between wild-type and delta TCRKO mice. These studies indicate that mice depleted of alpha beta but not of gamma delta T cells are resistant to mortality in an acutely lethal model of CLP. The depletion of NK cells caused further survival benefit in alpha beta T cell-deficient mice. These findings suggest that alpha beta T and NK cells mediate or facilitate CLP-induced inflammatory injury.