Multiple sclerosis is a demyelinating disease associated with an inflammatory immune response in the CNS. Theiler's murine encephalomyelitis virus (TMEV)-induced demyelinating disease is a relevant mouse model for the study of multiple sclerosis. TMEV infection of susceptible mice leads to a persistent virus infection of the CNS which contributes to development of demyelinating disease. We have previously shown that the innate immune response can affect the development and progression of demyelinating disease. In the current studies, we determined that the predominant infiltrating cells during the innate immune response are CD11b+Ly6C+ cells. CD11b+Ly6C+ cells are immature myeloid cells that have exited the bone marrow without maturing and have been shown to suppress CD4 + and CD8+ T cell responses. Therefore, we wanted to determine what role these cells play in development and progression of demyelinating disease. TMEV-infected mice depleted of CD11b+Ly6C + cells during the innate immune response developed a reduced demyelinating disease which was associated with a decreased myelin-specific CD4+ T cell response and a decreased inflammatory immune response in the CNS. TMEV-infected mice depleted of CD11b+Ly6C+ cells had increased virus-specific CD4+ and CD8+ T cell responses during early virus infection associated with increased expression of IFN-γ and IL-17 and decreased expression of IL-10 in the CNS. These results suggest that CD11b+Ly6C+ cells which infiltrate into the CNS during the innate immune response are myeloidderived suppressor cells that suppress virus-specific T cell responses and contribute to the development of demyelinating disease.