The role of Eos in T cell function (P1059)

Abstract

Abstract Eos, an Ikaros family transcription factor, is preferentially expressed in T regulatory cells (Tregs). Although previous studies have demonstrated that the elimination of Eos by siRNA in Tregs resulted in the loss of their suppressive function both in vitro and in vivo, Tregs from mice with a global deletion of Eos suppress normally in vitro and in the IBD model in vivo. While non-activated T conventional (Tconv) cells fail to express Eos, Eos expression is rapidly upregulated following TCR activation in vitro. TCR activated Tconv cells from Eos deficient (-/-) mice proliferate poorly, but make normal amounts of IL-2. The diminished proliferative response is secondary to a defect in the upregulation of CD25 that is accompanied by a decrease in p-STAT5 and p-S6 levels. Surprisingly, Eos-/- mice develop more severe EAE compared to wild type (WT) mice. Mixed chimeras between WT and EOS-/- bone marrow donors also develop very severe EAE. A greater number of Eos-/- CD4+ T cells than WT CD4+ T cells can be detected in the CNS and they produce higher levels of IL-17 than WT CD4+ T cells. Increased IL-17 production by Eos-/- CD4+ T cells correlates with their defect in IL-2 signaling. While WT Tregs can be detected in the CNS of the chimeric mice, Eos-/- Tregs are not detectable. These studies raise the possibility that Eos negatively regulates the production of IL-17 in Tconv, and may also play an important role in the migration of Tconvs and Tregs.