TY - JOUR
T1 - The role of cellular immune response in Theiler's virus-induced central nervous system demyelination
AU - Njenga, M. Kariuki
AU - Marques, Cristina
AU - Rodriguez, Moses
N1 - Funding Information:
This research was supported by the P01-NS 38468 and NS 32129 grants from the National Institutes of Health and a grant from the Academic Health Center of the University of Minnesota. We thank Rebecca LaRue, Jeremy Alley, and Laurie Brewer for their technical support.
PY - 2004/2
Y1 - 2004/2
N2 - Theiler's murine encephalomyelitis virus (TMEV) persists in spinal cord white matter of susceptible mice (e.g., SJL/J), resulting in chronic inflammation and demyelination. Reconstitution of severe combined immunodeficient (SCID) mice with CD4+ T- or CD8+ T-lymphocytes results in extensive TMEV-induced demyelination, and depletion of CD8+ T-lymphocytes in the early or late phase of the disease decreases the extent of demyelination, indicating that the cellular immune response against the virus plays a key role in myelin destruction. In susceptible mice, the demyelinated lesions are characterized by infiltration of a large numbers of B- and T-lymphocytes; whereas in mice resistant to TMEV-induced demyelination (e.g., C57BL/6), virus clearance requires infiltration of between 2.9×105 and 5.7×105 CD8+ T-lymphocytes and between 3.4×105 and 6.1×105 CD4+ T-lymphocytes per mouse in the brain 5-9 days post infection. Transgenic expression of capsid proteins of TMEV abrogates resistance in C56BL/6 mice, rendering the mice susceptible to TMEV persistence and demyelination. Comparison of the kinetics of virus replication and B- and T-lymphocyte infiltration in mice lacking key adhesion molecules (L-selectin (L-sel-/-), P-selectin (P-sel-/-), intracellular adhesion molecule-1 (ICAM-1-/-), or leukocyte function-associated antigen-1 (LFA-1-/-)) demonstrates a role for individual adhesion molecules in recruitment of immune cells into central nervous system (CNS), but the role is not significant to prevent eventual virus clearance.
AB - Theiler's murine encephalomyelitis virus (TMEV) persists in spinal cord white matter of susceptible mice (e.g., SJL/J), resulting in chronic inflammation and demyelination. Reconstitution of severe combined immunodeficient (SCID) mice with CD4+ T- or CD8+ T-lymphocytes results in extensive TMEV-induced demyelination, and depletion of CD8+ T-lymphocytes in the early or late phase of the disease decreases the extent of demyelination, indicating that the cellular immune response against the virus plays a key role in myelin destruction. In susceptible mice, the demyelinated lesions are characterized by infiltration of a large numbers of B- and T-lymphocytes; whereas in mice resistant to TMEV-induced demyelination (e.g., C57BL/6), virus clearance requires infiltration of between 2.9×105 and 5.7×105 CD8+ T-lymphocytes and between 3.4×105 and 6.1×105 CD4+ T-lymphocytes per mouse in the brain 5-9 days post infection. Transgenic expression of capsid proteins of TMEV abrogates resistance in C56BL/6 mice, rendering the mice susceptible to TMEV persistence and demyelination. Comparison of the kinetics of virus replication and B- and T-lymphocyte infiltration in mice lacking key adhesion molecules (L-selectin (L-sel-/-), P-selectin (P-sel-/-), intracellular adhesion molecule-1 (ICAM-1-/-), or leukocyte function-associated antigen-1 (LFA-1-/-)) demonstrates a role for individual adhesion molecules in recruitment of immune cells into central nervous system (CNS), but the role is not significant to prevent eventual virus clearance.
KW - Adhesion molecules
KW - Cellular immune response
KW - Demyelination
KW - Theiler's syndrome
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U2 - 10.1016/j.jneuroim.2003.10.042
DO - 10.1016/j.jneuroim.2003.10.042
M3 - Article
C2 - 14741431
AN - SCOPUS:1642575045
SN - 0165-5728
VL - 147
SP - 73
EP - 77
JO - Journal of neuroimmunology
JF - Journal of neuroimmunology
IS - 1-2
ER -