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(en) INTRODUCTION: The transcription factor HELIOS is primarily known for its expression in CD4 regulatory T cells, both in humans and mice. In mice, HELIOS is found in exhausted CD8 T cells. However, information on human HELIOS+ CD8 T cells is limited and conflicting. METHODS: In this study, we characterized by flow cytometry and transcriptomic analyses human HELIOS+ CD8 T cells. RESULTS: These T cells primarily consist of memory cells and constitute approximately 21% of blood CD8 T cells. In comparison with memory HELIOS- T-BEThigh CD8 T cells that displayed robust effector functions, the memory HELIOS+ T-BEThigh CD8 T cells produce lower amounts of IFN-γ and TNF-α and have a lower cytotoxic potential. We wondered if these cells participate in the immune response against viral antigens, but did not find HELIOS+ cells among CD8 T cells recognizing CMV peptides presented by HLA-A2 and HLA-B7. However, we found HELIOS+ CD8 T cells that recognize a CMV peptide presented by MHC class Ib molecule HLA-E. Additionally, a portion of HELIOS+ CD8 T cells is characterized by the expression of CD161, often used as a surface marker for identifying TC17 cells. These CD8 T cells express TH17/TC17-related genes encoding RORgt, RORa, PLZF, and CCL20. DISCUSSION: Our findings emphasize that HELIOS is expressed across various CD8 T cell populations, highlighting its significance beyond its role as a transcription factor for Treg or exhausted murine CD8 T cells. The significance of the connection between HELIOS and HLA-E restriction is yet to be understood.
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Neyens, D., Hirsch, T., Abdel Aziz Issa Abdel Hadi, A., Dauguet, N., Vanhaver, C., Bayard, A., Wildmann, C., Luyckx, M., Squifflet, J.-L., D’Hondt, Q., Duhamel, C., Huaux, A., Montiel, V., Dechamps, M., & van der Bruggen, P. (2023). HELIOS-expressing human CD8 T cells exhibit limited effector functions. Frontiers in Immunology, 14, 1308539 [1-15]. https://doi.org/10.3389/fimmu.2023.1308539 (Original work published 2023)