HELIOS identifies an HLA-E-restricted CD8 T cell population and is associated with low effector functions.

The transcription factor HELIOS is primarily known for its expression in CD4 regulatory T cells. In mice, HELIOS is also found in exhausted CD8 T cells. However, information on human HELIOS+ CD8 T cells is limited and conflicting. In this study, we characterized human HELIOS+ CD8 T cells, and found that these cells comprise approximately 21% of blood CD8 T cells. The majority of HELIOS+ CD8 T cells are memory cells, and some of them recognize peptides presented by the MHC class Ib molecule HLA-E. Memory HELIOS- T-BEThigh CD8 T cells displayed robust effector functions, while HELIOS+ T-BEThigh CD8 T cells produce low amounts of IFN-? and TNF-? and have a lower cytotoxic potential. Additionally, a portion of HELIOS+ CD8 T cells express TH17/TC17-related genes ROR?t, ROR?, PLZF, CD161 and CCL20. Thus, HELIOS is expressed in various CD8 T cell populations, including T-BEThigh cells with lower effector functions, and TC17 cells. It remains to be understood why so many individuals maintain in their blood high amounts of HELIOS+ T-BEThigh CD8 T cells that produce low amounts of cytokines upon activation and what the connection between HELIOS and HLA-E restriction means. Overall design: PBMCs from donors activated or not in vitro for 5h with coated anti-CD3 and then FACS sorted before RNA sequencing to compare HELIOS+ vs HELIOS- CD8 T cells.