The balance between persistent virus infection and immune cells determines demyelination.
We addressed the contributions of persistent virus infection and immune cells to the pathogenesis of Theiler's virus-induced demyelination, a model for human multiple sclerosis. We developed a model involving the transfer of spleen cells into immunodeficient C.B-17-scid (SCID) mice, which normally die of overwhelming virus encephalitis without demyelination when infected with Theiler's virus. Adoptive transfer of nonimmune spleen cells from BALB/c mice into SCID mice resulted in the survival of all mice. However, these mice developed extensive demyelination and virus Ag/RNA persistence in the spinal cord white matter. The most demyelination was observed when mice received an intermediate number of spleen cells (1.8-7.5 x 10(6)), whereas too few cells (0.5 x 10(6)) did not ameliorate the SCID phenotype, and too many cells (30 x 10(6)) resulted in almost complete viral clearance with minimal demyelination. Adoptive transfer of spleen cells depleted of either CD4+ or CD8+ T cells produced vacuolar demyelination associated with virus persistence. In contrast, reconstitution with both CD4+ and CD8+ T cells produced less severe demyelination and partial clearance of virus. These experiments support the hypothesis that demyelination is the result of a balance between persistent virus infection and immune injury mediated by either CD4+ or CD8+ T cells.
Rodriguez
M
M
Department of Neurology, Mayo Clinic and Foundation, Rochester, MN 55905, USA.
Pavelko
K D
KD
Njenga
M K
MK
Logan
W C
WC
Wettstein
P J
PJ
D019264:Adoptive Transfer; D000818:Animals; D001921:Brain / Q000473:pathology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002908:Chronic Disease; D003711:Demyelinating Diseases / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D005260:Female; D008212:Lymphocyte Depletion; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D011051:Poliomyelitis / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D013116:Spinal Cord / Q000473:pathology; D017945:Theilovirus / Q000472:pathogenicity; D017735:Virus Latency