CD8 +Helios +T cells: A unique functional T cell subpopulation?

Abstract

Abstract The zinc finger protein, Helios, is a member of the Ikaros transcription factor family and is expressed in CD4 +T cells, CD8 +T cells and in some NK cells in both mice and humans. While it has been found to have a role in the homeostasis and suppressive function of CD4 +Foxp3 +T regulatory cells (Treg), its function in CD8 +T cells and NK cells is not well characterized. We have demonstrated that ~10–40% of CD8 +T cells from normal donors express Helios. Expression of Helios in CD8 +appears to be downregulated with TCR stimulation alone but is maintained in the presence of excess IL-2 signaling. Thus far, extensive flow cytometry studies have failed to show a correlation between Helios expression and any other surface or intracellular markers. Mouse CD8 +Helios +Ly-49 +T cells have been reported to inhibit the activation of B cells in germinal centers and have been claimed to be the CD8 +counterpart to CD4 +Treg. While these studies have been performed in mice, there is very little data to suggest that human CD8 +Helios +T cells exhibit T suppressor function. In humans, the killer-cell immunoglobulin-like receptors (KIRs), a family of transmembrane glycoproteins, are said to be the functional equivalent of the Ly49 proteins. KIR +CD8 +T cells have previously been said to highly express Helios and have a function in autoimmune conditions. Data we have obtained from a CITE-seq analysis has shown that Heliosexpression in CD8s is highly correlated with many NK-cell associated markers. This, along with data showing that these cells produce cytotoxic effector molecules, leads us to speculate that these cells have a role in immune suppression via cytotoxic killing of self-activated immune cells. This work was supported by the Intramural Research Program of NIAID, NIH. This work was supported by the Intramural Research Program of NIAID, NIH.