A fresh look at a neglected regulatory lineage: CD8⁺Foxp3⁺ Regulatory T cells

CD4⁺Foxp3⁺ Regulatory T cells (Tregs) are essential for maintaining self-tolerance and are increasingly recognised to have important roles in tissue homeostasis and repair. In the CD8 compartment an analogous Foxp3⁺ population is present, which shares phenotypic aspects with the more common CD4⁺Foxp3⁺Treg population. While oft neglected for their low frequency, there is increasing evidence that these CD8⁺Foxp3⁺ cells are bona fide regulatory cells, with both shared and distinct characteristics from their CD4⁺ analogue. Here we focus on the evidence for a regulatory function of CD8⁺Foxp3⁺ cells, and the potential unique role this neglected lineage may play in immune homeostasis and disease prevention.