Induction of global anergy rather than inhibitory Th2 lymphokines mediates posttrauma T cell immunodepression
Induction of global anergy rather than inhibitory Th2 lymphokines mediates posttrauma T cell immunodepression
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DOI：
10.1006/clim.2000.4879
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发表时间：
2000-07-01
影响因子：
8.6
通讯作者：
Miller-Graziano, CL
中科院分区：
文献类型：
--
作者：
De, AK;Kodys, KM;Miller-Graziano, CL
严重机械或热损伤后丝裂原诱导的 IL-2 和 IFN-γ 反应受到抑制，推测是由于 Th2 淋巴细胞的扩增以及伴随的 IL-4 和/或 IL-10 的过量产生所致。在这里，我们同时评估了创伤患者分离的 T 细胞在充分共刺激、抗原呈递细胞独立系统（抗 CD3 + 抗 CD4）中刺激后的增殖和 Th1（IFN-γ）与 Th2（IL-10、IL-4）淋巴因子的产生。增殖和 IL-2 产生抑制的 T 细胞同时失去了 IL-4、IL-10 和 IFN-γ 蛋白和 mRNA 反应。添加外源性IL-12并不能恢复IFNγ反应，但外源性IL-2部分恢复了IL-4、IFN-γ和IL-10的产生。尽管最初通过外源性 IL-2 或 PMA + 离子霉素刺激部分恢复，但持续无反应的患者 T 细胞甚至逐渐丧失这些淋巴因子和增殖反应。整体T细胞无反应性的发展并不是T细胞活力或蛋白质合成丧失的结果，因为它对应于CD11b表达上调的无反应性T细胞的优势，但CD28和CD3表达下调。因此，分离的 T 细胞变得无反应的创伤后患者亚群经历了逐渐恶化的整体无反应性，这不是由 Th2 淋巴因子产生增加介导的，而可能是由于 T 细胞无法通过 TCR 触发或 Ca2+ 动员来激活。 (C) 2000 年学术出版社。
Depressed mitogen-induced IL-2 and IFN-gamma responses after severe mechanical or thermal injury are postulated to result from an expansion of Th2 lymphocytes with concomitant excessive production of IL-4 and/or IL-10. Here, we simultaneously assessed proliferation and Th1 (IFN-gamma) versus Th2 (IL-10, IL-4) lymphokine production in trauma patients' isolated T cells stimulated in a costimulation sufficient, antigen presenting cell independent system (anti CD3 + anti-CD4). T cells with depressed proliferation and IL-2 production simultaneously lost IL-4, IL-10, and IFN-gamma protein and mRNA responses. Exogenous IL-12 addition did not restore IFN gamma responses, but exogenous IL-2 partially restored IL-4, IFN-gamma, and IL-10 production. Although initially partially restored by exogenous IL-2 or stimulation with PMA + ionomycin, patient T cells with persisting anergy progressively lost even these lymphokine and proliferative responses. Development of global T cell anergy was not a result of lost T cell viability or protein synthesis, since it corresponded to predominance of anergic T cells with upregulated expression of CD11b, but downregulated CD28 and CD3 expression. Thus, the subset of posttrauma patients whose isolated T cells become unresponsive experienced progressively worsening global anergy, mediated not by an increased production of Th2 lymphokines, but possibly by T cell incapacity to be activated through TCR triggering or Ca2+ mobilization. (C) 2000 Academic Press.