Because the CD8+ T cell response is pivotal for TMEV clearance (35, 43), it was investigated whether a non-TMEV reactive CD8+ T cell repertoire (OT-I) or a numerically reduced CD8+ T cell repertoire without appropriate CD4+ T cell help (OT-II) would lead to increased susceptibility for TMEV-infection, possibly causing virus persistence and demyelination, as it was previously seen in CD8-deficient mice (49–52). This evidence concerns the gene CD4 and infection.