Co-expression of Foxp3 and Helios facilitates the identification of human T regulatory cells in health and disease.

ABSTRACT: Foxp3 is regarded as the major transcription factor for T regulatory (T_reg) cells and expression of Foxp3 is used to identify and quantitate Treg cells in mouse models. However, several studies have demonstrated that human CD4⁺ T conventional (T_conv) cells activated in vitro by T cell receptor (TCR) stimulation can express Foxp3. This observation has raised doubt as to the suitability of Foxp3 as a T_reg marker in man. Helios, a member of the Ikaros gene family, has been shown to be expressed by 80-90% of human Foxp3⁺ T_reg cells and can potentially serve as a marker of human T_reg. Here, we confirm that Foxp3 expression is readily upregulated by T_conv upon TCR stimulation in vitro, while Helios expression is not altered. More importantly, we show that Foxp3 expression is not elevated by stimulation of hT_conv in a humanized mouse model of graft versus host disease (GVHD) and in patients with a wide variety of acute and chronic inflammatory diseases including sickle cell disease, acute and chronic GVHD, systemic lupus erythematosus, as well as critical COVID-19. In all patients studied, an excellent correlation was observed between the percentage of CD4⁺ T cells expressing Foxp3 and the percentage expressing Helios. Taken together, these studies demonstrate that Foxp3 is not induced upon T_conv cell activation in vivo and that Foxp3 expression alone can be used to quantitate T_reg cells in humans. Nevertheless, the combined use of Foxp3 and Helios expression provides a more reliable approach for the characterization of T_reg in humans.

SUBMITTER: Morina L 

PROVIDER: S-EPMC10282999 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature