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
M. Vainiene et al., 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, Journal of neuroscience research, 45(4), 1996, pp. 475-486
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.