Enhanced susceptibility to Theiler's virus-induced demyelinating disease in perform-deficient mice

Theiler's virus induces immune-mediated demyelinating disease similar to hu man MS in susceptible mice. Though the MHC class II-restricted T cell respo nse is critical, susceptibility/resistance is also associated with a MHC cl ass I haplotype. Here we report that perforin-deficient C57BL/6 mice (pKO) are susceptible to demyelination and develop clinical disease. The levels o f primary demyelination, proliferation, Th1 responses, and viral load were also markedly enhanced. In addition, immunization of pKO mice with UV-inact ivated virus further enhanced clinical incidence and accelerated the diseas e course. Thus, perforin is most likely involved in viral clearance, hence protection from the disease. (C) 2001 Elsevier Science B.V. All rights rese rved.