Linked Life Data

12626579

Source:http://linkedlifedata.com/resource/pubmed/id/12626579

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2003-3-10
pubmed:abstractText
CD8(+) T cells infiltrating the CNS control infection by the neurotropic JHM strain of mouse hepatitis virus. Differential susceptibility of infected cell types to clearance by perforin or IFN-gamma uncovered distinct, nonredundant roles for these antiviral mechanisms. To separately evaluate each effector function specifically in the context of CD8(+) T cells, pathogenesis was analyzed in mice deficient in both perforin and IFN-gamma (PKO/GKO) or selectively reconstituted for each function by transfer of CD8(+) T cells. Untreated PKO/GKO mice were unable to control the infection and died of lethal encephalomyelitis within 16 days, despite substantially higher CD8(+) T cell accumulation in the CNS compared with controls. Uncontrolled infection was associated with limited MHC class I up-regulation and an absence of class II expression on microglia, coinciding with decreased CD4(+) T cells in CNS infiltrates. CD8(+) T cells from perforin-deficient and wild-type donors reduced virus replication in PKO/GKO recipients. By contrast, IFN-gamma-deficient donor CD8(+) T cells did not affect virus replication. The inability of perforin-mediated mechanisms to control virus in the absence of IFN-gamma coincided with reduced class I expression. These data not only confirm direct antiviral activity of IFN-gamma within the CNS but also demonstrate IFN-gamma-dependent MHC surface expression to guarantee local T cell effector function in tissues inherently low in MHC expression. The data further imply that IFN-gamma plays a crucial role in pathogenesis by regulating the balance between virus replication in oligodendrocytes, CD8(+) T cell effector function, and demyelination.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0022-1767
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
170
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3204-13
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:12626579-Acute Disease, pubmed-meshheading:12626579-Adoptive Transfer, pubmed-meshheading:12626579-Animals, pubmed-meshheading:12626579-CD8-Positive T-Lymphocytes, pubmed-meshheading:12626579-Central Nervous System Viral Diseases, pubmed-meshheading:12626579-Coronavirus Infections, pubmed-meshheading:12626579-Cytotoxicity, Immunologic, pubmed-meshheading:12626579-Encephalomyelitis, pubmed-meshheading:12626579-Histocompatibility Antigens Class I, pubmed-meshheading:12626579-Histocompatibility Antigens Class II, pubmed-meshheading:12626579-Interferon-gamma, pubmed-meshheading:12626579-Membrane Glycoproteins, pubmed-meshheading:12626579-Mice, pubmed-meshheading:12626579-Mice, Inbred BALB C, pubmed-meshheading:12626579-Mice, Inbred C57BL, pubmed-meshheading:12626579-Mice, Knockout, pubmed-meshheading:12626579-Murine hepatitis virus, pubmed-meshheading:12626579-Perforin, pubmed-meshheading:12626579-Pore Forming Cytotoxic Proteins, pubmed-meshheading:12626579-Up-Regulation
pubmed:year
2003
pubmed:articleTitle
Perforin-mediated effector function within the central nervous system requires IFN-gamma-mediated MHC up-regulation.
pubmed:affiliation
Department of Neurology, Keck School of Medicine, University of California, Los Angeles, CA 90033, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't