NEONATAL INJECTION OF LEWIS RATS WITH RECOMBINANT V-BETA-8.2 INDUCES T-CELL BUT NOT B-CELL TOLERANCE AND INCREASED SEVERITY OF EXPERIMENTALAUTOIMMUNE ENCEPHALOMYELITIS

In Lewis rats with experimental autoimmune encephalomyelitis (EAE) med iated by V beta 8.2 effector cells, anti-idiotypic T cells and antibod ies could be boosted by injection of V beta 8.2 peptides, inducing bot h T cells and antibodies that reduced the severity and shortened the c ourse of disease, However, EAE in Lewis rats is self-limiting, and we sought to determine if the anti-idiotypic response contributed to the natural recovery process, In a previous study, we found that adult tol erance induced to one of the regulatory idiotopes, V beta 8.2-44-54, c aused worsening of EAE, implicating response to this epitope in recove ry from EAE, However, neonatally-induced tolerance to V beta 8.2-44-54 did not alter the course of EAE, suggesting either compensation by ad ditional V beta 8.2 determinants, or mechanistic differences in toleri zation protocols, In this report, we reevaluate the role of V beta 8.2 determinants in recovery from EAE, using two recombinant V beta 8.2 c onstructs to induce neonatal tolerance to the comprehensive set of V b eta 8.2 epitopes prior to adult induction of EAE, We found that neonat al exposure to either of the recombinant V beta 8.2 molecules induced ''split'' tolerance - specific T cell tolerance but enhanced antibody responses - and a more severe course of EAE, In contrast, neonatal exp osure to a V beta 8.2+ T cell hybridoma or a control protein did not i nduce T cell tolerance to V beta 8.2 determinants and did not alter th e EAE disease course, These results are consistent with those obtained by inducing adult tolerance, and suggest that our previous result (no rmal recovery from EAE in rats neonatally tolerized to V beta 8.2-44-5 4) was probably due to a compensatory response to other V beta 8.2 det erminants, In both studies, the data clearly implicate T cell recognit ion of V beta 8.2 determinants in the natural EAE recovery process. (C ) 1996 Wiley-Liss, Inc.