Innate myeloid cells especially neutrophils and their extracellular traps are known to promote intravascular coagulation and thrombosis formation in infections and various other conditions. Innate myeloid cell dependent fibrin formation can support systemic immunity while its dysregulation enhances the severity of infectious diseases. Less is known about the immune mechanisms preventing dysregulation of fibrin homeostasis in infection. During experimental systemic infections local fibrin deposits in the liver microcirculation cause rapid arrest of CD4+ T cells. Arrested T helper cells mostly represent Th17 cells that partially originate from the small intestine. Intravascular fibrin deposits activate mouse and human CD4+ T cells which can be mediated by direct fibrin - CD4+ T cell interactions. Activated CD4+ T cells suppress fibrin deposition and microvascular thrombosis by directly counteracting coagulation activation by neutrophils and classical monocytes. T cell activation, which is initially triggered by IL- 12p40- and MHC-II dependent mechanisms, enhances intravascular fibrinolysis via LFA-1. Moreover, CD4+ T cells disfavor the association of the fibrinolysis inhibitor TAFI with fibrin whereby fibrin deposition is increased by TAFI in the absence but not presence of T cells. In human infections thrombosis development is inversely related to microvascular levels of CD4+ T cells. Thus, fibrin promotes LFA-1 dependent T helper cell activation in infections which drives a negative feedback cycle that rapidly restricts intravascular fibrin and thrombosis development.

中文翻译：

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CD4+ T 细胞和血管内纤维蛋白在感染中的相互调节。

已知先天性骨髓细胞，尤其是中性粒细胞及其细胞外陷阱，可在感染和各种其他病症中促进血管内凝血和血栓形成。先天性骨髓细胞依赖性纤维蛋白形成可以支持全身免疫，而其失调会加剧传染病的严重性。关于预防感染中纤维蛋白稳态失调的免疫机制知之甚少。在实验性全身感染期间，肝脏微循环中的局部纤维蛋白沉积导致 CD4+ T 细胞快速停滞。被抑制的 T 辅助细胞主要代表部分源自小肠的 Th17 细胞。血管内纤维蛋白沉积物激活小鼠和人类 CD4+ T 细胞，这可以通过直接纤维蛋白 - CD4+ T 细胞相互作用介导。活化的 CD4+ T 细胞通过直接对抗中性粒细胞和经典单核细胞的凝血激活来抑制纤维蛋白沉积和微血管血栓形成。 T 细胞激活最初由 IL-12p40 和 MHC-II 依赖性机制触发，通过 LFA-1 增强血管内纤维蛋白溶解。此外，CD4+T细胞不利于纤维蛋白溶解抑制剂TAFI与纤维蛋白的结合，由此在T细胞不存在但不存在的情况下TAFI增加纤维蛋白沉积。在人类感染中，血栓形成与微血管 CD4+ T 细胞水平呈负相关。因此，纤维蛋白在感染中促进 LFA-1 依赖性 T 辅助细胞活化，从而驱动负反馈循环，迅速限制血管内纤维蛋白和血栓形成的发展。