Inhibition of E protein activity facilitates the quiescence exit of naïve CD4+ T cells through modulating PI3K-AKT signaling and TCR microcluster formation

Abstract

Many aspects remain elusive of the mechanisms governing T cell quiescence. Here we show that E protein activity helps to establish a quiescent program in naïve T cells. Decreased E protein activity, as the consequence of enforced expression of an Id1 transgene, led to the accumulation of CD4⁺CD44^hi T cells. The naïve CD4⁺ T cells from this transgenic strain mounted a vigorous proliferative response upon TCR stimulation, as a result of direct inhibition of E protein activity. Transcriptome analyses demonstrated that Id1-tg naïve CD4⁺ T cells exhibited a transcriptional profile characteristic of activated CD4⁺ T cells, with particular enrichment in the gene set related to PI3K-AKT signaling. Western blot analysis confirmed low but constitutive activation of this pathway. Moreover, the Id1-tg CD4⁺ T cells displayed enhanced formation of TCR microcluster. Taken together, these data support that downregulation of E protein activity facilitates the exit of naïve T cells from quiescence.

Keywords: E protein activity; Naïve CD4(+) T cells; PI3K signaling pathway; Quiescence.