Development and functions of tissue resident memory T cells during EAE

Benaroya Research Inst At Virginia Mason, Seattle WA

Investigators

Abstract

Project Summary Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS) characterized by demyelination, axonal loss, and progressive disability. The disease can follow a relapsing remitting or a more chronic course. Similarly, experimental autoimmune encephalomyelitis (EAE) models are characterized by CNS inflammation and demyelination, and each recapitulate some aspects of MS. Although there is a wealth of knowledge regarding the association of different circulating T helper (Th) subsets with multiple sclerosis (MS), there is a paucity of information regarding the characteristics and functions of tissue resident memory T cells (TRM) which have been recently identified in the central nervous system (CNS) and the cerebrospinal fluid (CSF) of MS patients. To begin to address this gap, we have used a newly developed mouse strain to identify, track, characterize and eliminate TRMs during the course of experimental autoimmune encephalomyelitis (EAE). We propose that autoreactive CNS CD4+ TRM express a unique set of markers that distinguish them from other circulating central memory T cells and play an important role in disease progression. Using our newly developed tools, we will characterize the distribution, kinetic and characteristics of CD4+ TRM cells during EAE, establish whether they recirculate and participate in disease progression and relapses during EAE. The completion of this proposal will help us understand how memory T cells promote chronic autoimmunity and may lead to the development of novel therapies for MS.