T CELLS ARE CLONALLY EXPANDED IN THE SPINAL CORD OF TMEV-INFECTED
W.L. Lin3, J. Kuzmak1, J.R. Chang3, E. Zaczynska1,
C.D. Platsoucas3. Fels Institute Cancer
Res & Mol Biol1, Depts Anatomy &
Cell Biology, and Neurology2, Dept
Microbiology & Immunology3, Temple
Univ Sch Med, Philadelphia, PA.
encephalomyelitis virus (TMEV) causes in susceptible strains of
mice biphasic disease of the CNS. Early acute disease resembles
polioencephalomyelitis and it is resolved in about 20 days p.i.
Late chronic demyelinating disease appears approximately 30 days
p.i. and is characterized by extensive demyelination of the CNS.
Both early acute and late chronic demyelinating disease are
associated with the presence of mononuclear cell infiltrates in
the CNS of susceptible mice. T cells play a critical role in
clearance of the virus during early acute disease, however, their
role in late chronic demyelinating disease is poorly understood.
Little is known about the antigenic determinants, viral or host,
recognized by T cells infiltrating the CNS during demyelinating
disease. We have previously identified a b -chain T-cell
receptor (TCR) transcript, designated 451 (Vb 2.1 Db 2.1
Jb 2.1), that was clonally expanded in: (i) the brain
of TMEV-infected SJL mice with early acute disease, 8 days p.i.
(ii) the spinal cord of TMEV-infected SJL mice with late chronic
demyelinating disease, 170 days p.i. We amplified by Vb
2.1-specific PCR-TCR transcripts from the spinal cord of
TMEV-infected SJL mice 8, 25 and 39 days p.i. Sequence analysis
revealed that the 451 b -chain TCR transcript was also clonally
expanded in the spinal cord of TMEV-infected SJL mice with : (a)
early acute disease, 8 days p.i.; (b) 25 days p.i.; (c) late
chronic demyelinating disease, 39 days p.i. Additionally, 8% (8
of 96) of different b -chain TCR transcripts sequenced from the
spinal cord of TMEV-infected mice with late chronic demyelinating
disease, 170 days p.i., utilized CDR3 TCR motifs identical or
substantially homologous to those used by mouse, rat, or human
T-cell lines of clones specific for MBP. These transcripts may
have been generated in the process of epitope spreading. However,
none of the 52 b -chain TCR transcripts sequenced from the
CNS of TMEV-infected mice with late 39 days p.i. utilized these
CDR3 TCR motifs. These results suggest that T-cell clones
specific for host neuroantigens may not be responsible for
initiating demyelinating disease in TMEV-infected mice, although
as the demyelinating disease progresses, they may contribute in
propagating the disease.