Detrimental role for CD4+ T lymphocytes in murine diffuse peritonitis due to inhibition of local bacterial elimination
Detrimental role for CD4+ T lymphocytes in murine diffuse peritonitis due to inhibition of local bacterial elimination
复制标题
DOI：
10.1136/gut.2007.121616
复制
发表时间：
2008-02-01
期刊：
影响因子：
24.5
通讯作者：
Broeker, B. M.
中科院分区：
文献类型：
--
作者：
Busse, M.;Traeger, T.;Broeker, B. M.
背景：内源性肠道细菌肠道渗漏导致的腹部脓毒症是一种危及生命的疾病。在健康个体中，T 淋巴细胞在平衡对共生肠道菌群的免疫反应方面具有重要功能。目的：确定 T 淋巴细胞如何塑造弥漫性粪便腹膜炎的过程。方法：在结肠上升支架腹膜炎 (CASP)（一种临床相关的弥漫性腹膜炎小鼠模型）中，通过评估研究全身 T 细胞激活的动力学 的激活标记。然后用单克隆抗体清除CD4(+) T细胞，并测量存活率、细菌传播和细胞因子浓度。他克莫司阻断 T 细胞受体信号传导。结果：在弥漫性腹膜炎中，CD4(+) T 细胞（Foxp3(-) 和 Foxp3(+)）在数小时内全身参与，并上调 CTLA-4 和其他激活标记物。 CD4(+) T 细胞的耗竭增强了腹膜腔局部细菌的清除，减少了细菌传播并提高了存活率。与此同时，粒细胞和巨噬细胞向腹膜的迁移增加，表明 CD4(+) T 细胞抑制局部先天免疫反应。他克莫司阻断 T 细胞受体 (TCR) 信号传导并不影响该腹膜炎模型的存活，表明 CD4(+) T 淋巴细胞的抑制作用与 TCR 介导的抗原识别无关。结论：在共生肠道细菌引起的弥漫性腹膜炎中，CD4(+) T 淋巴细胞对局部腹膜炎产生净负效应。 抗菌防御，从而导致细菌传播和不良结果。
Background: Abdominal sepsis due to intestinal leakage of endogenous gut bacteria is a life-threatening condition. In healthy individuals, T lymphocytes have essential functions in balancing the immune response to the commensal gut flora.Aim: To determine how T lymphocytes shape the process of diffuse faecal peritonitis.Methods: In colon ascendens stent peritonitis (CASP), a clinically relevant mouse model of diffuse peritonitis, the kinetics of systemic T cell activation were investigated by assessment of activation markers. CD4(+) T cells were then depleted with monoclonal antibodies, and survival, bacterial dissemination and cytokine concentrations were measured. T cell receptor signalling was blocked with tacrolimus.Results: In diffuse peritonitis, CD4(+) T cells, both Foxp3(-) and Foxp3(+), became systemically involved within hours and upregulated CTLA-4 and other activation markers. Depletion of the CD4(+) T cells enhanced local bacterial clearance from the peritoneal cavity, reduced bacterial dissemination and improved survival. This was accompanied by increased immigration of granulocytes and macrophages into the peritoneum, indicating that CD4(+) T cells inhibit the local innate immune response. Blockade of T cell receptor (TCR) signalling by tacrolimus did not influence the survival in this peritonitis model, showing that the inhibitory effects of the CD4(+) T lymphocytes were independent of TCR-mediated antigen recognition.Conclusion: In diffuse peritonitis caused by commensal gut bacteria the CD4(+) T lymphocytes exert a net negative effect on the local anti-bacterial defence, and thereby contribute to bacterial dissemination and poor outcome.