Modulation of pathogenic T cells in EAE

Project Summary Multiple sclerosis (MS) is a disease characterized by inflammation, demyelination, and neurodegeneration of the central nervous system (CNS). Human genetic studies and adoptive transfer experiments in experimental autoimmune encephalomyelitis (EAE), an animal model of MS point to CD4+ T helper cells as important actors in the development and progression of CNS specific autoimmunity. IL-2 is a cytokine critical for maintaining T cell homeostasis, growth, and proliferation. IL-2 is predominantly produced by activated CD4+ T cells in lymphoid organs. However, this production is lost in most cells and only sustained in a unique fraction of CD4+ T cells. We have developed a novel tool which allow us to track, eliminate and study IL-2+ T cells during the development and progression of EAE. Here, we will determine the identity, characteristics and means to modulate IL-2+ T cells in the context of EAE development and progression and establish whether STAT1 limits IL-2+ T cells and their pathogenic functions. The completion of these studies will provide new insights on the function of IL-2+ cells during prolonged disease progression, establish whether the enhance STAT1 signaling can limit the pathogenic function of these cells, and identify markers of pathogenic IL-2+ T cells and pathways that can be further studied and targeted to limit the activity of these cells in the context of CNS autoimmunity.