Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan 48109-5602, USA.
Shock. 2011 Oct;36(4):396-401. doi: 10.1097/SHK.0b013e3182295f5f.
The contribution of the adaptive and innate immune systems to the pathogenesis and outcome of sepsis remains a fundamental yet controversial question. Here, we use mice lacking the recombination activating gene 1 (Rag-1) to study the role of T and B cells in sepsis after cecal ligation and puncture (CLP). Spleens of Rag-1 mice were atrophic and completely devoid of CD3 T cells and CD19 B cells. Wild-type mice and Rag-1 mice (both on a C57BL/6J background) underwent CLP or sham surgery. Both wild-type and Rag-1 mice developed clinical signs of sepsis within the first day after CLP. This included severe hypothermia as measured by a decrease in body surface temperature and organ dysfunction as detected by plasma increases in blood urea nitrogen and lactate dehydrogenase levels. Survival curves of wild-type and Rag-1 mice after CLP were superimposable, with 35% survival in the wild-type group and 27% survival in the Rag-1 group, respectively (not significant, P = 0.875). Using multiplex bead-based assays, the mediator concentrations for 23 cytokines and chemokines were measured in plasma of wild-type and Rag-1 mice 8 h after CLP or sham surgery. Compared with sham surgery mice, the highest mediator levels were observed for granulocyte colony-stimulating factor, keratinocyte chemoattractant, IL-6, monocyte chemotactic protein 1, and IL-10. Levels for most mediators were unaffected by the absence of T and B lymphocytes. Only the concentrations of IL-6 and IL-17 were found to be significantly lower in Rag-1 mice compared with wild-type mice. In conclusion, the absence of T and B cells in the CLP model used does not appear to affect the acute outcome of severe sepsis.
适应性免疫系统和固有免疫系统对脓毒症发病机制和转归的贡献仍然是一个基本但有争议的问题。在这里,我们使用缺乏重组激活基因 1(Rag-1)的小鼠来研究 T 和 B 细胞在盲肠结扎和穿刺(CLP)后脓毒症中的作用。Rag-1 小鼠的脾脏萎缩,完全缺乏 CD3 T 细胞和 CD19 B 细胞。野生型小鼠和 Rag-1 小鼠(均为 C57BL/6J 背景)接受 CLP 或假手术。野生型和 Rag-1 小鼠在 CLP 后第 1 天内均出现脓毒症的临床症状。这包括通过体表温度下降测量的严重低体温和通过血浆中血尿素氮和乳酸脱氢酶水平升高检测到的器官功能障碍。CLP 后野生型和 Rag-1 小鼠的生存曲线重叠,野生型组的存活率为 35%,Rag-1 组的存活率为 27%(无显著性差异,P=0.875)。使用多重珠基测定法,在 CLP 或假手术后 8 小时测量野生型和 Rag-1 小鼠血浆中 23 种细胞因子和趋化因子的介质浓度。与假手术小鼠相比,观察到最高的介质水平为粒细胞集落刺激因子、角质形成细胞趋化因子、IL-6、单核细胞趋化蛋白 1 和 IL-10。大多数介质的水平不受 T 和 B 淋巴细胞缺失的影响。只有 IL-6 和 IL-17 的浓度在 Rag-1 小鼠中比野生型小鼠明显更低。总之,在使用的 CLP 模型中缺乏 T 和 B 细胞似乎不会影响严重脓毒症的急性结局。