Transgenic Expression of Theiler's Murine Encephalomyelitis Virus Genes inH-2^bMice Inhibits Resistance to Virus-Induced Demyelination

Anticapsid Immunity Level, Not Viral Persistence Level, Correlates with the Progression of Theiler's Virus-Induced Demyelinating Disease in Viral P1-Transgenic Mice

“…Overall, T-cell proliferation levels for the epitopes by splenic and LN CD4 ϩ T cells from B6 P1-Tg mice were only 23 and 12% of the responses by their littermates, indicating that CD4 ϩ T-cell responses to P1 neoself antigens were effectively tolerized. In contrast, CD4 ϩ T-cell responses to capsid epitopes (VP1 233-250 , VP2 74-86 , and VP3 [24][25][26][27][28][29][30][31][32][33][34][35][36][37] ) in SJL P1-Tg mice were as much as 64 to 75% of the responses by their littermates. These results indicate that the Tg expression of the TMEV P1 region induces the weak tolerance of proliferative responses to capsid-specific CD4 ϩ Tcell epitopes in SJL P1-Tg mice, in contrast to the strong tolerance seen in B6 P1-Tg mice.…”

“…At 9 days postimmunization (pi), lymph node (LN) and spleen cells were stimulated with capsid peptides recognized by CD4 ϩ T cells. B6 P1-Tg mice displayed severe unresponsiveness (P Ͻ 0.001) in their proliferative responses to capsid epitopes (VP2 206-220 and VP4 [25][26][27][28][29][30][31][32][33][34][35][36][37][38] ) compared to those from their littermates ( Fig. 2A).…”

“…(A) CNS-infiltrating MNCs isolated from TMEV-infected mice were restimulated with the indicated mixture of CD4 ϩ T-cell-specific epitopes (S mix for cells from B6 mice, VP2 206-220 and VP4 [25][26][27][28][29][30][31][32][33][34][35][36][37][38] ; S mix for cells from SJL mice, VP1 233-250 , VP2 [74][75][76][77][78][79][80][81][82][83][84][85][86] , and VP3 [24][25][26][27][28][29][30][31][32][33][34][35][36][37]. CON represents control cultures similarly incubated with PBS.…”

“…Nevertheless, our results clearly indicate that viral persistence alone is not sufficient to induce TMEV-IDD in B6 P1-Tg mice. A group of investigators previously showed that B10 VP1-Tg mice are susceptible to TMEV-induced demyelination (31). These Tg mice displayed VP1-specific CD8 ϩ T-cell tolerance after TMEV infection but similar levels of lymphocyte proliferation and virus-specific antibody responses after repeated immunizations with UV-TMEV.…”

A Subgenomic Segment of Theiler's Murine Encephalomyelitis Virus RNA Causes Demyelination

“…There are two prior reports concerning the generation of mice carrying DA subgenomic constructs as transgenes (12,29). In contrast to the DA/Cre mouse, neither of the other transgenic mice developed a phenotype, presumably because of the differences in the transgene and the level and timing of the transgene's expression.…”