Roles of CD1d‐restricted Vα 14+ NKT cells in Theiler's virus infection, a viral model for multiple sclerosis

Abstract

Most murine natural killer (NK) T cells express an invariant Vα 14 T cell receptor and are CD1d‐restricted. We investigated the contribution of NKT cells in an animal model for multiple sclerosis (MS), Theiler's murine encephalomyelitis virus (TMEV) infection. First, we treated susceptible SJL/J mice with an antibody against Vα 14 during TMEV infection. Treatment during the early stage of infection delayed the onset of clinical disease with relatively higher interleukin (IL)‐4 production. In contrast, treatment during the late stage or weekly injections resulted in more severe demyelination with higher virus persistence. Next, we compared TMEV infection in wild‐type versus CD1d KO mice in the background of TMEV‐resistant BALB/c mice. Although no wild‐type mice developed demyelination, 20 and 60% of CD1d KO mice developed demyelination at 3 and 5 weeks after infection, respectively. TMEV‐infected CD1d KO mice showed higher IL‐4 production and TMEV‐specific lymphoproliferative responses, compared with wild‐type mice. These results suggest that NKT cells could modulate inflammatory demyelinating disease by altering the cytokine profile and virus‐specific immune responses. This work was supported by the University of Utah (Funding Incentive Seed Grant to IT) and the National Institute of Health (NS34497 to RSF).