Innate CD4+ T cells associated with development of virus- induced demyelinating disease (INC1P.362)

Abstract

Abstract Theiler’s murine encephalomyelitis virus (TMEV) infection of susceptible mice results in a persistent infection in the central nervous system (CNS) that leads to the development of a chronic progressive demyelinating disease associated with a pro-inflammatory immune response. TMEV- induced demyelinating disease serves as a mouse model for multiple sclerosis. TMEV infection of resistant mice leads to clearance of the virus from the CNS without development of demyelinating disease. We have previously shown that the innate immune response to TMEV directly affects development of demyelinating disease in susceptible mice. We recently identified a population of CD4+ T cells that infiltrate into the CNS during the innate immune response to TMEV in susceptible mice. Most interestingly, the resistant mice infected with TMEV do not have innate immune infiltration of CD4+ T cells into the CNS. The CNS infiltrating innate immune CD4+ T cells in the TMEV- infected susceptible mice were NK1.1-, αβ+ and CD3+. The innate immune CD4+ T cells expressed high levels of IL-17A and IFNγ but low levels of IL-22. Furthermore, susceptible mice expressed high levels of IL-23, IL-1β, and IL-6 during the innate immune response to TMEV which promotes IL-17A expression in CD4+ T cells. Therefore, the innate immune response in susceptible mice promotes the infiltration of innate CD4+ T cells into the CNS which express pro-inflammatory cytokines associated with development of demyelinating disease.