Regulatory T (T reg) cells are a specialized sublineage of T lymphocytes that suppress autoreactive T cells. Functional studies of T reg cells in vitro have defined multiple suppression mechanisms, and studies of T reg–deficient humans and mice have made clear the important role that these cells play in preventing autoimmunity. However, many questions remain about how T reg cells act in vivo. Specifically, it is not clear which suppression mechanisms are most important, where T reg cells act, and how they get there. To begin to address these issues, we sought to identify T reg cells in zebrafish, a model system that provides unparalleled advantages in live-cell imaging and high-throughput genetic analyses. Using a FOXP3 orthologue as a marker, we identified CD4-enriched, mature T lymphocytes with properties of T reg cells. Zebrafish mutant for foxp3a displayed excess T lymphocytes, splenomegaly, and a profound inflammatory phenotype that was suppressed by genetic ablation of lymphocytes. This study identifies T reg–like cells in zebrafish, providing both a model to study the normal functions of these cells in vivo and mutants to explore the consequences of their loss.

调节性T（T reg）细胞是抑制自身反应性T细胞的T淋巴细胞的专门亚系。体外T reg细胞的功能研究定义了多种抑制机制，对T reg缺乏的人和小鼠的研究明确了这些细胞在预防自身免疫中的重要作用。然而，关于T reg细胞如何在体内发挥作用，仍然存在许多问题。具体而言，尚不清楚哪种抑制机制最重要，T reg细胞在哪里起作用以及如何到达那里。为了开始解决这些问题，我们试图鉴定斑马鱼中的T reg细胞，该模型系统在活细胞成像和高通量遗传分析中提供了无与伦比的优势。使用FOXP3直向同源物作为标志物，我们鉴定了具有T reg细胞特性的富含CD4的成熟T淋巴细胞。foxp3a的斑马鱼突变体显示出过量的T淋巴细胞，脾肿大和深刻的炎性表型，该表型被淋巴细胞的遗传消融所抑制。这项研究鉴定了斑马鱼中的Treg样细胞，为研究这些细胞在体内的正常功能提供了一个模型，并为突变体提供了探索其损失后果的模型。