Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840, USA.
J Immunol. 2013 Jun 1;190(11):5485-95. doi: 10.4049/jimmunol.1202951. Epub 2013 May 3.
Friend virus infection of mice induces the expansion and activation of regulatory T cells (Tregs) that dampen acute immune responses and promote the establishment and maintenance of chronic infection. Adoptive transfer experiments and the expression of neuropilin-1 indicate that these cells are predominantly natural Tregs rather than virus-specific conventional CD4(+) T cells that converted into induced Tregs. Analysis of Treg TCR Vβ chain usage revealed a broadly distributed polyclonal response with a high proportionate expansion of the Vβ5(+) Treg subset, which is known to be responsive to endogenous retrovirus-encoded superantigens. In contrast to the major population of Tregs, the Vβ5(+) subset expressed markers of terminally differentiated effector cells, and their expansion was associated with the level of the antiviral CD8(+) T cell response rather than the level of Friend virus infection. Surprisingly, the expansion and accumulation of the Vβ5(+) Tregs was IL-2 independent but dependent on TNF-α. These experiments reveal a subset-specific Treg induction by a new pathway.
友病毒感染小鼠诱导调节性 T 细胞（Tregs）的扩增和激活，从而抑制急性免疫反应，并促进慢性感染的建立和维持。过继转移实验和神经纤毛蛋白-1 的表达表明，这些细胞主要是天然 Tregs，而不是转化为诱导性 Tregs 的病毒特异性常规 CD4(+)T 细胞。对 Treg TCR Vβ 链使用的分析显示出广泛分布的多克隆反应，其中 Vβ5(+)Treg 亚群的比例显著扩增，已知该亚群对内源性逆转录病毒编码的超抗原有反应。与主要的 Treg 群体相比，Vβ5(+)亚群表达终末分化效应细胞的标志物，其扩增与抗病毒 CD8(+)T 细胞反应的水平而不是 Friend 病毒感染的水平相关。令人惊讶的是，Vβ5(+)Tregs 的扩增和积累不依赖于 IL-2，但依赖于 TNF-α。这些实验揭示了一种新途径的亚群特异性 Treg 诱导。
