Foxp3⁺CD8⁺ regulatory T cells: bona fide Tregs with cytotoxic function

Various mammalian CD8⁺ T cell subsets with regulatory properties are either formed through a thymus-dependent mechanism or induced under various experimental protocols and referred to as CD8⁺ regulatory T cells (Tregs). CD8⁺ Tregs maintain distinct functions in the presence of CD4⁺ Tregs. This review focuses on the Foxp3⁺CD8⁺ Treg subset, which is typically extremely rare in unmanipulated mice and healthy humans under steady-state conditions. However, they can be induced and expanded for transplantation, autoimmune diseases, cancer, viral infections, and T cell receptor transgenic adoptive cell transfer models. Here, we summarize recent research progress related to this population, including the identification of phenotypic markers, induction determinants, and functional activities. Additionally, we discuss advances in manipulating Foxp3⁺CD8⁺ Tregs in autoimmunity and transplantation.