The present study was undertaken to determine whether the mice depleted of αβ or γδ T cells show resistance to acute polymicrobial sepsis caused by cecal ligation and puncture (CLP). T-cell receptor β knockout (βTCRKO) and T-cell receptor δ knockout (δTCRKO) mice were used. An additional group of mice was treated with an antibody against the αβ T-cell receptor to induce αβ T-cell depletion; a subset of αβ T cell-deficient mice was also treated with anti-asialoGM1 to deplete natural killer (NK) cells. The mice underwent CLP and were monitored for survival, temperature, acid-base balance, bacterial counts, and cytokine production. The βTCRKO mice and the wild-type mice treated with anti-β T-cell receptor (anti-TCRβ) antibody showed improved survival after CLP compared with wild-type mice. The treatment of αβ T cell-deficient mice with anti-asialoGM1further improved survival after CLP, especially when the mice were treated with imipenem. The improved survival observed in αβ 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 δTCRKO 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 δTCRKO mice. These studies indicate that mice depleted of αβ but not of γδ T cells are resistant to mortality in an acutely lethal model of CLP. The depletion of NK cells caused further survival benefit in αβ T cell-deficient mice. These findings suggest that αβ T and NK cells mediate or facilitate CLP-induced inflammatory injury.
ASJC Scopus subject areas
- Emergency Medicine
- Critical Care and Intensive Care Medicine