Departamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, Argentina.
Centro de Investigaciones en Bioquímica Clínica e Inmunología, CONICET, Córdoba, Argentina.
Front Immunol. 2018 Nov 5;9:2555. doi: 10.3389/fimmu.2018.02555. eCollection 2018.
While it is now acknowledged that CD4 T cells expressing CD25 and Foxp3 (Treg cells) regulate immune responses and, consequently, influence the pathogenesis of infectious diseases, the regulatory response mediated by Treg cells upon infection by was still poorly characterized. In order to understand the role of Treg cells during infection by this protozoan parasite, we determined in time and space the magnitude of the regulatory response and the phenotypic, functional and transcriptional features of the Treg cell population in infected mice. Contrary to the accumulation of Treg cells reported in most chronic infections in mice and humans, experimental infection was characterized by sustained numbers but decreased relative frequency of Treg cells. The reduction in Treg cell frequency resulted from a massive accumulation of effector immune cells, and inversely correlated with the magnitude of the effector immune response as well as with emergence of acute immunopathology. In order to understand the causes underlying the marked reduction in Treg cell frequency, we evaluated the dynamics of the Treg cell population and found a low proliferation rate and limited accrual of peripheral Treg cells during infection. We also observed that Treg cells became activated and acquired a phenotypic and transcriptional profile consistent with suppression of type 1 inflammatory responses. To assess the biological relevance of the relative reduction in Treg cells frequency observed during infection, we transferred differentiated Treg cells at early moments, when the deregulation of the ratio between regulatory and conventional T cells becomes significant. Intravenous injection of Treg cells dampened parasite-specific CD8 T cell immunity and affected parasite control in blood and tissues. Altogether, our results show that limited Treg cell response during the acute phase of infection enables the emergence of protective anti-parasite CD8 T cell immunity and critically influences host resistance.
虽然现在已经承认表达 CD25 和 Foxp3（Treg 细胞）的 CD4 T 细胞调节免疫反应，并因此影响传染病的发病机制，但 Treg 细胞在感染时介导的调节反应仍未得到充分描述。为了了解 Treg 细胞在感染这种原生动物寄生虫时的作用，我们在时间和空间上确定了调节反应的幅度以及感染小鼠中 Treg 细胞群体的表型、功能和转录特征。与大多数在小鼠和人类中发生的慢性感染中报道的 Treg 细胞积累相反，实验性感染的特征是 Treg 细胞数量持续增加，但相对频率降低。Treg 细胞频率的降低是由于效应免疫细胞的大量积累所致，并且与效应免疫反应的幅度以及急性免疫病理学的出现呈负相关。为了了解导致 Treg 细胞频率明显降低的原因，我们评估了 Treg 细胞群体的动态，发现感染期间 Treg 细胞的增殖率低且外周 Treg 细胞的积累有限。我们还观察到 Treg 细胞被激活并获得了与抑制 1 型炎症反应一致的表型和转录特征。为了评估在感染期间观察到的 Treg 细胞频率相对降低的生物学相关性，我们在调节性和常规 T 细胞之间的比例发生显著失调的早期时刻转移分化的 Treg 细胞。静脉注射 Treg 细胞可抑制寄生虫特异性 CD8 T 细胞免疫，并影响血液和组织中的寄生虫控制。总的来说，我们的结果表明，在感染的急性阶段 Treg 细胞反应有限，使保护性抗寄生虫 CD8 T 细胞免疫得以出现，并严重影响宿主抵抗力。
