Much of our understanding of central nervous system (CNS) immunity has been gained from models involving pathological inflammation. Attenuated rabies viruses (RABV) are unique tools to study CNS immunity in the absence of conventional inflammatory mechanisms, as they spread from the site of inoculation to the CNS trans-axonally, thereby bypassing the blood-brain barrier (BBB), and are cleared without neutrophil or monocyte infiltration. To better understand the role of CD4 T cell subsets in the clearance of the virus from CNS tissues we examined the development of antiviral immunity in wild type (WT) and T-bet knock-out mice (T-bet−/−), which lack Th1 cells. Early control of RABV replication in the CNS tissues of WT mice is associated with the production of IFNγ, with antiviral effects likely mediated through the enhanced expression of type I interferons. Interestingly, IFN-α and −γ are overexpressed in the infected T-bet−/− by comparison with WT CNS tissues and the initial control of RABV infection is similar. Ultimately, attenuated RABV are cleared from the CNS tissues of WT mice by antibody locally produced by the activities of infiltrating T and B cells. While T and B cell infiltration into the CNS of infected T-bet−/− mice is comparable, their activities are not, the consequence being delayed, low level antibody production and prolonged RABV replication. More importantly, neither T-bet−/− mice immunized with an attenuated virus, nor WT mice with Th2 RABV-specific immunity induced by immunization with inactivated virus, are protected, in the long term, against challenge with a pathogenic RABV.