CD8⁺ Regulatory T Cell - A Mystery to Be Revealed

Regulatory T cells (Treg) are essential to maintain immune homeostasis and prevent autoimmune disorders. While the function and molecular regulation of Foxp3⁺CD4⁺ Tregs are well established, much of CD8⁺ Treg biology remains to be revealed. Here, we will review the heterogenous subsets of CD8⁺ T cells have been named "CD8⁺ Treg" and mainly focus on CD122^hiLy49⁺CD8⁺ Tregs present in naïve mice. CD122^hiLy49⁺CD8⁺ Tregs, which depends on transcription factor Helios and homeostatic cytokine IL-15, have been established as a non-redundant regulator of germinal center (GC) reaction. Recently, we have demonstrated that TGF-β (Transforming growth factor-β) and transcription factor Eomes (Eomesodermin) are essential for the function and homeostasis of CD8⁺ Tregs. In addition, we will discuss several open questions regarding the differentiation, function and true identity of CD8⁺ Tregs as well as a brief comparison between two regulatory T cell subsets critical to control GC reaction, namely CD4⁺ T_FR (follicular regulatory T cells) and CD8⁺ Tregs.