Chronic relapsing experimental allergic encephalomyelitis: Correlation of circulating lymphocyte fluctuations with disease activity in suppressed and unsuppressed animals

Abstract

Groups of juvenile Strain 13 guinea pigs sensitized for chronic relapsing experimental allergic encephalomyelitis (EAE) with isogeneic central nervous system (CNS) tissue in complete Freund's adjuvant (CFA) were either left to develop late-onset chronic EAE (unsuppressed), or given a series of injections of bovine myelin basic protein (MBP) in incomplete Freund's adjuvant (IFA) to suppress the disease. All unsuppressed animals developed disease and all suppressed animals remained healthy over a 27-month period of study. Some unsuppressed and suppressed animals were rechallenged with CNS tissue in CFA 12 or 26 months post-inoculation (PI). Unsuppressed animals all became sick 2–4 weeks after rechallenge, while rechallenged, suppressed animals were protected, indicating that the suppression was permanent. Pathologic findings in the CNS complemented the clinical changes. Circulating lymphocyte studies were performed on animals from all groups. Early (active, high-affinity rosetting) T cell levels in unsuppressed animals showed significant decreases during exacerbations ( P < 0.01) and normal values during remissions. After rechallenge, circulating early T cells decreased in unsuppressed animals with the development of signs. In suppressed animals, early T cells showed significant elevations during, and for a short time after, the period of suppressive injections, and normal values afterwards. These levels did not change significantly after rechallenge. Late (total, 24 hour rosetting) T cell and B cell values showed minor fluctuations only which did not correlate with disease activity. These results indicate that chronic relapsing EAE can be successfully suppressed with MBP in IFA, that this suppression is permanent and that the immunologic findings presented correlate well with the clinical and pathologic facets of the disease. The findings are presented in terms of their relevance to multiple sclerosis.