Role of cervical lymph nodes in autoimmune encephalomyelitis in the Lewis rat

Abstract

Lymphocytes enter the central nervous system (CNS) in response to virus infections and in autoimmune diseases, such as multiple sclerosis (MS), but the origin of such lymphocytes is unclear. This study investigates the role of the cervical lymph nodes as a source of lymphocytes involved in experimental autoimmune disease of the brain. Acute active experimental autoimmune encephalomyelitis (EAE) is used as a model for the autoimmune aspects of MS and is characterized by lymphocyte and monocyte invasion and microglial activation, mainly in the spinal cord, 12-15 days post-inoculation (dpi) of antigen. Few lesions occur in the cerebral hemispheres in acute EAE, but a cryolesion to the surface of the brain 8 dpi results in a six-fold enhancement of cerebral EAE. The present study tests the hypothesis that cervical lymphadenectomy will reduce the enhancement of cerebral EAE induced by a cryolesion. Acute EAE was induced in 25 Lewis rats and a cryolesion to the brain, 8 dpi, in 16 rats was immediately followed by either cervical lymphadenectomy (n = 8) or sham lymphadenectomy (n = 8). The severity of EAE at 15 dpi, in the brain and spinal cord, was evaluated using immunocytochemistry for T lymphocytes (W3/13) and MHC class II expression (OX6). The results of the study showed that cervical lymphadenectomy reduced the level of cerebral EAE induced by a cryolesion by 40 per cent when compared with the sham-operated animals (P < 0.01). This suggests that cervical lymph nodes play a pivotal role in the induction of EAE in the brain, possibly as a site for 'priming' T cells to target the brain. Investigation of the interrelationships between cervical lymph nodes and the brain in man may lead to new therapeutic strategies for multiple sclerosis.