Linked Life Data

9736651

Source:http://linkedlifedata.com/resource/pubmed/id/9736651

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
18
pubmed:dateCreated
1998-10-2
pubmed:abstractText
In this study we demonstrate perforin-mediated cytotoxic effector function is necessary for viral clearance and may directly contribute to the development of neurologic deficits after demyelination in the Theiler's murine encephalomyelitis virus (TMEV) model of multiple sclerosis. We previously demonstrated major histocompatability complex (MHC) class I-deficient (beta2m-deficient) mice with an otherwise resistant genotype develop severe demyelination with minimal neurologic disease when chronically infected with TMEV. These studies implicate CD8(+) T cells as the pathogenic cell in the induction of neurologic disease after demyelination. To determine which effector mechanisms of CD8(+) T cells, granule exocytosis or Fas ligand expression, play a role in the development of demyelination and clinical disease, we infected perforin-deficient, lpr (Fas mutation), and gld (Fas ligand mutation) mice with TMEV. Perforin-deficient mice showed viral persistence in the CNS, chronic brain pathology, and demyelination in the spinal cord white matter. Perforin-deficient mice demonstrated severely impaired MHC class I-restricted cytotoxicity against viral epitopes, but normal MHC class II-restricted delayed-type hypersensitivity responses to virus antigen. Despite demyelination, virus-infected perforin-deficient mice showed only minimal neurologic deficits as indicated by clinical disease score, activity monitoring, and footprint analysis. Perforin- and MHC class II-deficient mice (with functional CD8(+) T cells and perforin molecules and an H-2(b) haplotype) had comparable demyelination and genotype, however, only the latter showed severe clinical disease. Gld and lpr mice demonstrated normal TMEV-specific cytotoxicity and maintained resistance to TMEV-induced demyelinating disease. These studies implicate perforin release by CD8(+) T cells as a potential mechanism by which neurologic deficits are induced after demyelination.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0270-6474
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
18
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
7306-14
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed-meshheading:9736651-Animals, pubmed-meshheading:9736651-Antigens, CD95, pubmed-meshheading:9736651-Chronic Disease, pubmed-meshheading:9736651-Demyelinating Diseases, pubmed-meshheading:9736651-Disease Models, Animal, pubmed-meshheading:9736651-Exocytosis, pubmed-meshheading:9736651-Fas Ligand Protein, pubmed-meshheading:9736651-Female, pubmed-meshheading:9736651-Histocompatibility Antigens Class I, pubmed-meshheading:9736651-Male, pubmed-meshheading:9736651-Membrane Glycoproteins, pubmed-meshheading:9736651-Mice, pubmed-meshheading:9736651-Mice, Inbred C57BL, pubmed-meshheading:9736651-Mice, Mutant Strains, pubmed-meshheading:9736651-Microscopy, Electron, pubmed-meshheading:9736651-Multiple Sclerosis, pubmed-meshheading:9736651-Mutation, pubmed-meshheading:9736651-Neurons, pubmed-meshheading:9736651-Perforin, pubmed-meshheading:9736651-Poliomyelitis, pubmed-meshheading:9736651-Pore Forming Cytotoxic Proteins, pubmed-meshheading:9736651-Spinal Cord, pubmed-meshheading:9736651-T-Lymphocytes, Cytotoxic, pubmed-meshheading:9736651-Theilovirus
pubmed:year
1998
pubmed:articleTitle
Perforin-dependent neurologic injury in a viral model of multiple sclerosis.
pubmed:affiliation
Department of Immunology, Mayo Clinic and Foundation, Rochester, Minnesota 55905, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't