Memory Cells Specific for Myelin Oligodendrocyte Glycoprotein Govern the Transfer of Experimental Autoimmune Encephalomyelitis (101.26)

Abstract Multiple sclerosis (MS) is a chronic, inflammatory disease of the central nervous system thought to be initiated by CD4+ T cells specific for myelin antigens. Experimental autoimmune encephalomyelitis (EAE), a model of MS, is induced in susceptible mouse strains by immunization with myelin antigens such as myelin oligodendrocyte glycoprotein (MOG). MOG35-55-specific T cell receptor transgenic (2D2) mice are susceptible to EAE following immunization with MOG peptide. To better understand the role of T cells in EAE initiation, we explored several approaches for effecting adoptive transfer of EAE using 2D2 T cells. Surprisingly, despite robust proliferation and production of IFN-γ and IL-17 following a variety of culture conditions, EAE was not transferred. Only when 2D2 whole splenocyte preparations contained CD44+ T cells and were Th1-differentiated using MOG peptide and IL-12 did they reliably transfer EAE. Further, we found that CD44hiCD62Llo effector/memory CD4+ T cells are likely responsible for disease transfer due to up-regulation of the adhesion molecule CD44 following differentiation. We also observed a sex dimorphism in 2D2 mice with males transferring more severe EAE, associated with a larger population of effector/memory CD4+ T cells in males compared to females. Given the importance of MOG in MS pathogenesis, mechanistic insights into adoptively transferred EAE by MOG-specific Th1 cells could prove valuable in MS research.