CD8+ Regulatory T Cell – A Mystery to Be Revealed
Shruti Mishra, Saranya Srinivasan, Chaoyu Ma, Nu Zhang
Abstract
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 hi Ly49 + CD8 + Tregs present in naïve mice. CD122 hi Ly49 + 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.