The role of cellular immune response in Theiler's virus-induced central nervous system demyelination.
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 x 10(5) and 5.7 x 10(5) CD8(+) T-lymphocytes and between 3.4 x 10(5) and 6.1 x 10(5) 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.
Njenga
M Kariuki
MK
Department of Veterinary Pathobiology, University of Minnesota, 1971 Commonwealth Avenue, St. Paul, MN 55108, USA. njeng001@tc.umn.edu
Marques
Cristina
C
Rodriguez
Moses
M
D000818:Animals; D001769:Blood / Q000821:virology; D001921:Brain / Q000276:immunology / Q000821:virology; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism / Q000821:virology; D015815:Cell Adhesion Molecules / Q000235:genetics; D002494:Central Nervous System Infections / Q000150:complications / Q000276:immunology / Q000821:virology; D003711:Demyelinating Diseases / Q000209:etiology* / Q000276:immunology* / Q000821:virology; D005434:Flow Cytometry / Q000379:methods; D007111:Immunity, Cellular; D008198:Lymph Nodes / Q000276:immunology / Q000821:virology; D016169:Lymphocyte Function-Associated Antigen-1 / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D019007:P-Selectin / Q000235:genetics; D013154:Spleen / Q000276:immunology / Q000821:virology; D017945:Theilovirus / Q000472:pathogenicity*
D015815:Cell Adhesion Molecules; D016169:Lymphocyte Function-Associated Antigen-1; D019007:P-Selectin