Mice depleted of αβ but not γδ T cells are resistant to mortality caused by cecal ligation and puncture
Mice depleted of αβ but not γδ T cells are resistant to mortality caused by cecal ligation and puncture
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DOI：
10.1097/shk.0b013e31802b5d9f
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发表时间：
2007-05-01
期刊：
影响因子：
3.1
通讯作者：
Sherwood, Edward R.
中科院分区：
文献类型：
--
作者：
Enoh, Victor T.;Lin, Scott H.;Sherwood, Edward R.
本研究旨在确定αβ或γδT细胞耗尽的小鼠是否表现出对盲肠结扎穿刺（CLIP）引起的急性多种微生物败血症的抵抗力。使用T细胞受体β敲除（β TCRKO）和T细胞受体δ敲除（δ TCRKO）小鼠。另外一组小鼠接受了针对 αβT 细胞受体的抗体治疗，以诱导 αβT 细胞耗竭；一部分 alpha beta T 细胞缺陷小鼠也接受了抗asialoGM1 治疗，以消除自然杀伤 (NK) 细胞。这些小鼠接受了 CILP，并监测其存活率、体温、酸碱平衡、细菌计数和细胞因子的产生。与野生型小鼠相比，β TCRKO 小鼠和用抗 P T 细胞受体（抗 TCR β）抗体治疗的野生型小鼠在 CLP 后表现出更好的存活率。用抗asialoGM1治疗αβT细胞缺陷小鼠，进一步提高了CLP后的存活率，特别是当小鼠用亚胺培南治疗时。在 alpha beta T 细胞缺陷小鼠中观察到的生存率提高与体温降低、酸碱平衡改善以及促炎细胞因子白细胞介素 (IL) 6 和巨噬细胞炎症蛋白 (MIP) 2 的产生减少有关。与野生型对照相比，delta TCRKO 小鼠的总体生存率没有提高。野生型和 delta TCRKO 小鼠血浆中 IL-6 和 MIP-2 的浓度以及组织中细胞因子 mRNA 的表达没有显着差异。这些研究表明，在 CLP 急性致死模型中，αβ T 细胞耗尽但 γ δ T 细胞未耗尽的小鼠能够抵抗死亡。 NK 细胞的消耗导致 αβ T 细胞缺陷小鼠的进一步生存获益。这些发现表明 αβT 细胞和 NK 细胞介导或促进 CLP 诱导的炎症损伤。
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.