Development and functions of tissue resident memory T cells during EAE

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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.