The functional role of Helios in CD4+ T cells

Abstract

Abstract The transcription factor Helios is expressed in the majority of Foxp3+ Regulatory T cells (Treg), where it plays an essential role in Treg function. Loss of Helios in the Treg population induces systemic autoimmunity, marked by CD4 and CD8 hyperproliferation, enhanced germinal center formation, and systemic immune activation. Helios is also expressed in a small subset of conventional CD4 +T cells. However, when Helios is deleted in all CD4 cells, conventional and Treg, by crossing the mice to CD4Cre, this phenotype is abrogated, indicating that Helios must also play a significant role in the function of conventional CD4 +T cells. In order to examine specific subsets of CD4 +memory cells, we performed single cell transcriptome analysis of CD44 himemory cells from WT mice and mice with the CD4 specific deletion of Helios. Characterization of the CD44 hiHelios +population showed that Helios expression changed dramatically with age, so cells from young (5–6 weeks) and old (5–6 months) mice were included in the analysis. Both longitudinal (young vs old) and cross-sectional (WT vs KO) comparisons were made, with emphasis placed on cross-sectional comparisons at old age. The sequencing results indicated significant transcriptomic and numeric shifts in multiple subpopulations of the analyzed splenocytes, including the almost complete loss of one cluster in both the young and old Helios deficient mice. Taken together, the observed transcriptomic and clustering changes may explain the role Helios plays in the abrogation of autoimmunity in our model and may provide a starting point for us to analyze its function in other biological pathways. This work was supported by the Intramural Research Program of NIAID, NIH This work was supported by the Intramural Research Program of NIAID, NIH