Immune memory in the CNS (P1177)

Abstract

Abstract Due to specialized neurovasculature, referred to as the blood-brain barrier (BBB), CNS tissues are immunologically privileged and only infiltrated by lymphocytes under certain circumstances. One of these is the clearance of attenuated rabies virus (RABV) from the CNS which is dependent upon CD4 T and B cell entry into CNS tissues and local production of virus neutralizing antibody (VNA). Despite spread to the CNS, these processes do not occur during wild-type RABV infection. Differences in the spread and induction of immunity to different RABV in mice allow us to determine if immune effector accumulation in CNS tissues results in the establishment of immune memory in this location. The attenuated recombinant RABV TriGAS has a severely curtailed ability to spread and does not reach the CNS when administered to the gastrocnemius. Mice infected with TriGAS via this route are fully protected against a peripheral challenge with wild-type RABV but not against intra-nasal infection with the same virus. Protection against a CNS challenge with wild-type RABV is only established by vaccination regimens that deliver RABV-specific immune effectors to the CNS. Lymphocytes remain in the CNS for extended periods of time following clearance of attenuated virus and appear to rapidly divide upon local challenge with wild-type RABV. This suggests that these cells may represent CNS resident immune memory cells capable of reactivating to produce VNA upon local challenge.