Neonatal exposure of TCR BV8S2 transgenic mice to recombinant TCR BV8S2 results in reduced T cell proliferation and elevated antibody response to BV8S2, and increased severity of EAE.
Transgenic (Tg) mouse models are unique tools for investigating regulatory mechanisms of the immune system. Mice bearing a T cell receptor (TCR) BV8S2 transgene derived from an encephalitogenic T cell clone are highly susceptible to experimental autoimmune encephalomyelitis (EAE), a T cell-mediated neurological disorder. Although the pathogenesis of EAE is not yet fully understood, TCR-specific regulatory T cells seem to play a role in its remission and/or recovery process. In previous studies, we showed that immunization of BV8S2 Tg mice with recombinant BV8S2 protein induced TCR-specific T cells and protection against EAE, clearly indicating the persistence of a functional TCR regulatory network in spite of the highly skewed T cell repertoire. To further investigate the natural regulatory role of TCR-specific T cells, we evaluated the effect on EAE of inducing neonatal tolerance to heterologous (rat) and homologous BV8S2 proteins in Tg mice. Neonatal exposure to rat BV8S2 protein induced "split" tolerance, characterized by decreased T cell proliferation but increased antibody responses to both rat and mouse BV8S2 proteins that are known to be cross-reactive. When challenged as adults with an encephalitogenic emulsion, Tg mice tolerized with rat but not mouse BV8S2 protein developed more severe EAE compared to control mice. These results demonstrate that immunity to BV8S2 determinants in BV8S2 Tg mice is naturally induced and functions to limit the severity of EAE.
Siklodi
B
B
Biogal Pharmaceutical, Debrecen, Hungary.
Jacobs
R
R
Vandenbark
A A
AA
Offner
H
H
D000818:Animals; D000831:Animals, Newborn / Q000033:anatomy & histology* / Q000276:immunology*; D000906:Antibodies / Q000187:drug effects / Q000276:immunology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics* / Q000503:physiopathology*; D005982:Glutathione Transferase / Q000494:pharmacology; D007108:Immune Tolerance / Q000502:physiology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic / Q000235:genetics*; D051381:Rats; D011917:Rats, Inbred Lew; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics* / Q000276:immunology; D011994:Recombinant Proteins; D012016:Reference Values; D013601:T-Lymphocytes / Q000187:drug effects; D019076:Transgenes / Q000235:genetics*
D000906:Antibodies; D016693:Receptors, Antigen, T-Cell, alpha-beta; D011994:Recombinant Proteins; D005982:Glutathione Transferase