ROLE OF CERVICAL LYMPH-NODES IN AUTOIMMUNE ENCEPHALOMYELITIS IN THE LEWIS RAT

Lymphocytes enter the central nervous system (CNS) in response to viru s infections and in autoimmune diseases, such as multiple sclerosis (M S), but the origin of such lymphocytes is unclear. This study investig ates the role of the cervical lymph nodes as a source of lymphocytes i nvolved 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 m onocyte invasion and microglial activation, mainly in the spinal cord, 12-15 days post-inoculation (dpi) of antigen. Few lesions occur in th e cerebral hemispheres in acute EAE, but a cryolesion to the surface o f the brain 8 dpi results in a six-fold enhancement of cerebral EAE. T he present study tests the hypothesis that cervical lymphadenectomy wi ll reduce the enhancement of cerebral EAE induced by a cryolesion. Acu te EAE was induced in 25 Lewis rats and a cryolesion to the brain, 8 d pi, in 16 rats was immediately followed by either cervical lymphadenec tomy (n=8) or sham lymphadenectomy (n=8). The severity of EAE at 15 dp i, in the brain and spinal cord, was evaluated using immunocytochemist ry for T lymphocytes (W3/13) and MHC class II expression (OX6). The re sults of the study showed that cervical lymphadenectomy reduced the le vel of cerebral EAE induced by a cryolesion by 40 per cent when compar ed with the sham-operated animals (P<0.01). This suggests that cervica l 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. Invest igation of the interrelationships between cervical lymph nodes and the brain in man may lead to new therapeutic strategies for multiple scle rosis. (C) 1997 by John Wiley & Sons, Ltd.