In Lewis rats with experimental autoimmune encephalomyelitis (EAE) mediated by Vβ8.2 effector cells, anti-idiotypic T cells and antibodies could be boosted by injection of Vβ8.2 peptides, inducing both T cells and antibodies that reduced the severity and shortened the course 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 tolerance induced to one of the regulatory idiotopes, Vβ8.2-44-54, caused worsening of EAE, implicating response to this epitope in recovery from EAE. However, neonatally-induced tolerance to Vβ8.2-44-54 did not alter the course of EAE, suggesting either compensation by additional Vβ8.2 determinants, or mechanistic differences in tolerization protocols. In this report, we reevaluate the role of Vβ8.2 determinants in recovery from EAE, using two recombinant Vβ8.2 constructs to induce neonatal tolerance to the comprehensive set of Vβ8.2 epitopes prior to adult induction of EAE. We found that neonatal exposure to either of the recombinant Vβ8.2 molecules induced 'split' tolerance - specific T cell tolerance but enhanced antibody responses and a more severe course of EAE. In contrast, neonatal exposure to a Vβ8.2+ T cell hybridoma or a control protein did not induce T cell tolerance to Vβ8.2 determinants and did not alter the EAE disease course. These results are consistent with those obtained by inducing adult tolerance, and suggest that our previous result (normal recovery from EAE in rats neonatally tolerized to Vβ8.2-44-54) was probably due to a compensatory response to other Vβ8.2 determinants. In both studies, the data clearly implicate T cell recognition of Vβ8.2 determinants in the natural EAE recovery process.
|Original language||English (US)|
|Number of pages||12|
|Journal||Journal of Neuroscience Research|
|State||Published - Jan 1 1996|
ASJC Scopus subject areas
- Cellular and Molecular Neuroscience