Enhanced susceptibility to Theiler's virus-induced demyelinating disease in perforin-deficient mice.
Theiler's virus induces immune-mediated demyelinating disease similar to human MS in susceptible mice. Though the MHC class II-restricted T cell response is critical, susceptibility/resistance is also associated with a MHC class I haplotype. Here we report that perforin-deficient C57BL/6 mice (pKO) are susceptible to demyelination and develop clinical disease. The levels of primary demyelination, proliferation, Th1 responses, and viral load were also markedly enhanced. In addition, immunization of pKO mice with UV-inactivated virus further enhanced clinical incidence and accelerated the disease course. Thus, perforin is most likely involved in viral clearance, hence protection from the disease.
Palma
J P
JP
Department of Microbiology-Immunology, Northwestern University Medical School, 303 East Chicago Avenue, 60611, Chicago, IL, USA
Lee
H G
HG
Mohindru
M
M
Kang
B S
BS
Dal Canto
M
M
Miller
S D
SD
Kim
B S
BS
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology; D004195:Disease Models, Animal; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology; D015994:Incidence; D008562:Membrane Glycoproteins / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009103:Multiple Sclerosis / Q000235:genetics / Q000276:immunology / Q000821:virology*; D054353:Perforin; D011051:Poliomyelitis / Q000235:genetics* / Q000276:immunology; D052899:Pore Forming Cytotoxic Proteins; D013116:Spinal Cord / Q000276:immunology / Q000473:pathology / Q000821:virology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000821:virology; D017945:Theilovirus
D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D054353:Perforin