Innate immune CD11b+Gr-1+ cells, myeloid- derived suppressor cells, influence the adaptive immune response during demyelinating disease (137.6)

Abstract

Abstract Innate immune CD11b+Gr-1+ cells are a heterogeneous population of cells which include neutrophils and myeloid- derived suppressor cells (MDSC). CD11b+Gr-1+ cells that express Ly6C are MDSC which can directly suppress T cell responses. Theiler's murine encephalomyelitis virus (TMEV) is a mouse model of multiple sclerosis in which mice develop a chronic progressive demyelinating disease associated with a myelin- specific CD4+ T cell response. We have previously shown that the innate immune response directly affects the initiation and progression of demyelinating disease. Thus, we wanted to determine the role of CD11b+Gr-1+ cells in the innate immune response during TMEV- induced demyelinating disease. TMEV- infected mice had a large number of infiltrating CD11b+Gr-1+ cells composed of Ly6Chigh cells in the central nervous system (CNS) during the innate immune response. Depletion of Gr-1+ cells in TMEV-infected mice resulted in increased expression of IFNγ, IL-12, and IL-17 in the CNS during the innate immune response and altered development of demyelinating disease. Most importantly, CD11b+Gr-1+ cells suppressed the activation of CD4+ and CD8+ T cells in TMEV- infected mice. These results suggest that innate immune CD11b+Gr-1+ cells, specifically the MDSC, influence the adaptive immune response and modulate the development and progression of demyelinating disease. This work was supported by the National Multiple Sclerosis Society Grant RG3625.