Experimental autoimmune encephalomyelitis (EAE) is a demyelinating disease
of the central nervous system (CNS) that serves as a model for multiple scl
erosis (MS) in humans. In mice, EAE is mediated by Th1 type CD4(+) T cells
specific for various myelin proteins which migrate from the periphery to th
e CNS. Removal or blocking of CD4(+) cells before or shortly after disease
induction was shown to prevent disease onset and/or disease progression but
also results in general immune suppression. Most treatment regimens for au
toimmune diseases currently rely on general suppression of the T-cell compa
rtment most commonly by steroids. In this paper, an experimental, gene ther
apy-based model is presented in which susceptible mice are made resistant t
o EAE induction by specifically down-regulating an autoreactive T-cell popu
lation. By using a retroviral gene transfer protocol, normal B cells were g
enetically modified to constitutively express the SJL-specific proteolipid
(PLP) encephalitogenic determinant and then adoptively transferred into syn
geneic hosts. To ensure appropriate presentation of the exogenous encephali
togenic peptide in association with MHC class II, the encephalitogenic sequ
ence was fused to a lysosomal targeting sequence. Adoptive transfer of syng
eneic B cells expressing the PLP encephalitogenic determinant into normal,
naive, genetically susceptible mice induced PLP-specific unresponsiveness a
nd completely protected the majority (62% and 83% using an intermediate and
a high titer retroviral vector, respectively) of the animals from EAE indu
ction. The remaining animals had a delayed disease onset and/or lower disea
se severity. All protected mice expressed the exogenous gene in the spleen
as detected by reverse transcriptase-polymerase chain reaction. (C) 2001 by
The American Society of Hematology.