Regulation of CD4 T Cell Responses by the Transcription Factor Eomesodermin

Abstract

Central to the impacts of CD4 T cells, both positive in settings of infectious disease and cancer and negative in the settings of autoimmunity and allergy, is their ability to differentiate into distinct effector subsets with specialized functions. The programming required to support such responses is largely dictated by lineage-specifying transcription factors, often called ‘master regulators’. However, it is increasingly clear that many aspects of CD4 T cell immunobiology that can determine the outcomes of disease states involve a broader transcriptional network. Eomesodermin (Eomes) is emerging as an important member of this class of transcription factors. While best studied in CD8 T cells and NK cells, an increasing body of work has focused on impacts of Eomes expression in CD4 T cell responses in an array of different settings. Here, we focus on the varied impacts reported in these studies that, together, indicate the potential of targeting Eomes expression in CD4 T cells as a strategy to improve a variety of clinical outcomes.

Hypothesis of a CD137/Eomes activating axis for effector T cells in HPV oropharyngeal cancers

“…A CD137+/Eomes + axis has been described in several publications (Dhume et al 2022 ; Lupar et al 2015 ; Mittal et al 2018 ).…”

“…The identification of cells and their relationships to each other within the microenvironment could be specified on patient tissues via spatial single-cell RNA-sequencing or flow cytometry by time-of-flight. The activated profile of the cells would be enhanced by studying the methylation of genes coding for transcription factors such as FoxP3 + and Eomes by genome-wide analysis in relation to the expression of CD137/Eomes by T cells (CpG methylation analysis by bisulfite sequencing) (Dhume et al 2022 ). The markers and transcription factors studied correspond to a function or its regulation: activated Treg (CD4 + CD45RA-FoxP3 + CD15s+), Effectors CD4 + FoxP3 + T cells (CD4 + CD45RA-FoxP3 + Eomes+).…”