Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109.
J Immunol. 2014 Jan 15;192(2):683-90. doi: 10.4049/jimmunol.1202153. Epub 2013 Dec 11.
Regulatory T cells (Tregs) are well known for their role in dampening the immune responses to self-Ags and, thereby, limiting autoimmunity. However, they also must permit immune responses to occur against foreign infectious agents. Using a mouse model of West Nile virus infection, we examined the role of Tregs in the generation of effector and memory T cell responses in the secondary lymphoid organs, as well as the infected tissues. We found that Treg numbers and activation increased in both the secondary lymphoid organs and CNS postinfection. Using Foxp3(DTR) knock-in mice, we found that Treg-deficient mice had increased Ag-driven production of IFN-γ from both CD4(+) and CD8(+) T cells in the spleen and CNS during the effector phase. In mice lacking Tregs, there were greater numbers of short-lived effector CD8(+) T cells in the spleen during the peak of the immune response, but the memory CD8(+) T cell response was impaired. Specifically, we demonstrate that Treg-dependent production of TGF-β results in increased expression of CD103 on CD8(+) T cells, thereby allowing for a large pool of resident memory T cells to be maintained in the brain postinfection.
调节性 T 细胞（Tregs）因其在抑制自身抗原免疫反应中的作用而闻名，从而限制了自身免疫。然而，它们也必须允许针对外来感染因子的免疫反应发生。我们使用西尼罗河病毒感染的小鼠模型，研究了 Tregs 在次级淋巴器官以及感染组织中效应和记忆 T 细胞反应产生中的作用。我们发现，感染后 Tregs 的数量和激活在次级淋巴器官和中枢神经系统中均增加。使用 Foxp3(DTR)基因敲入小鼠，我们发现，在效应期，Treg 缺失小鼠的脾脏和中枢神经系统中 CD4(+)和 CD8(+)T 细胞的 IFN-γ产生增加。在缺乏 Tregs 的小鼠中，在免疫反应的高峰期，脾脏中短暂存活的效应 CD8(+)T 细胞数量增加，但记忆 CD8(+)T 细胞反应受损。具体而言，我们证明 Treg 依赖性 TGF-β的产生导致 CD8(+)T 细胞上 CD103 的表达增加，从而允许在感染后大脑中维持大量的驻留记忆 T 细胞。
