IMMUNOLOGICAL SIGNIFICANCE OF LYMPHATIC D RAINAGE OF THE BRAIN

Despite the evidence for immunological reactions in the human CNS, in viral encephalitis and in multiple sclerosis, connections between the brain and the immune system are poorly understood. In rodents, tracers injected into the interstitial fluid of the brain drain to the cervic al lymph nones by perivascular pathways in the brain and nasal lymphat ics. Similar pathways could serve as lymphatics in the human brain. In the present study, we test the hypothesis that lymphatic drainage of the brain and cervical lymph nodes play a key role in T-cell mediated immunity of the brain. Experimental allergic encephalomyelitis (EAE) w as induced in Lewis rats by the injection of guinea pig spinal cord ho mogenate in complete Freund's adjuvant into the foot pads. This result ed in paralysis of the hind limbs and infiltration of lymphocytes and microglial activation centred mainly on the spinal cord, little inflam mation was seen in the cerebrum. When a brain wound, in the form of cr yolesion, was inflicted on one cerebral hemisphere, 8 days after the i nduction of EAE, there was a 6-fold enhancement of EAE lesions in the brain. This enhancement was reduced by 40% cervical lymphadenectomy at the time of the cryolesion. These results suggest that cervical lymph nodes play a pivotal role in cerebral EAE and may be a major source o f brain-directed lymphocytes. If similar mechanisms apply in man, stud y of cervical lymphocytes and their manipulation could open new therap eutic avenues for the treatment of multiple sclerosis.