Chronic relapsing experimental autoimmune encephalomyelitis: Transient presence in blood of lymphocytes sensitised to encephalitogen at onset of inflammatory relapses

Abstract

Juvenile guinea pigs were immunised with homologous spinal cord and monitored daily over a 6-month period for neurological signs of chronic relapsing experimental autoimmune encephalomyelitis (CREAE). At various times animals were killed, numbers of leucocytes in their cerebrospinal fluid (CSF) quantified, and in vitro proliferative responses of blood lymphocytes to myelin basic protein (MBP) and its encephalitogenic nonapeptide (NP) determined. After recovering from initial acute clinical signs, animals suffered at least two major spontaneous relapses separated by remission periods of 4–5 weeks mean duration. In the early chronic phase, 5–12 weeks post-immunisation (pi), 63% of the animals recovered fully from relapses, whereas relatively irreversible neurological deficits predominated in the late chronic phase. During the acute and chronic phases, there was a highly significant correlation between clinical severity and CSF pleocytosis only in animals killed within 24 h of onset of a clinical exacerbation associated with more than 100 leucocytes/μl of CSF. Guinea pigs with this degree of CSF pleocytosis were defined as suffering an inflammatory relapse. Blood lymphocytes responsive to MBP and NP were detected only in animals killed at the onset of clinical signs of either the acute or an inflammatory relapse. This dynamic relationship suggests that migration of encephalitogen-responsive lymphocytes via the blood to the central nervous system could produce certain relapses in CREAE. However, the relative paucity of CSF leucocytes in most animals killed during relapses between 15–26 weeks pi suggests that other factors may elicit neurological exacerbations in the late chronic phase.