Source:http://linkedlifedata.com/resource/pubmed/id/19124736
Switch to
Predicate | Object |
---|---|
rdf:type | |
lifeskim:mentions | |
pubmed:issue |
2
|
pubmed:dateCreated |
2009-1-6
|
pubmed:abstractText |
A critical issue during severe respiratory infection is whether it is the virus or the host response that does the most damage. In this study, we show that endogenous 4-1BBL plays a critical role in protecting mice from severe effects of influenza disease. During mild respiratory influenza infection in which virus is rapidly cleared, the inducible costimulatory receptor 4-1BB is only transiently induced on lung T cells and 4-1BB ligand (4-1BBL) is completely dispensable for the initial CD8 T cell response and mouse survival. In contrast, during more severe respiratory influenza infection with prolonged viral load, 4-1BB expression on lung CD8 T cells is sustained, and 4-1BBL-deficient mice show decreased CD8 T cell accumulation in the lungs, decreased viral clearance, impaired lung function, and increased mortality. Transfer of an optimal number of naive Ag-specific T cells before infection protects wild-type but not 4-1BBL-deficient mice from an otherwise lethal dose of influenza virus. Transfer of T cells lacking the proapoptotic molecule Bim extends the lifespan of 4-1BBL-deficient mice by one to three days, suggesting that at least part of the role of 4-1BB/4-1BBL is to prolong effector cell survival long enough to clear virus. Intranasal delivery of 4-1BBL by recombinant adenovirus marginally improves survival of 4-1BBL-deficient mice at low dose, but exacerbates disease at high dose. These findings suggest a rationale for the evolutionary accumulation of inducible costimulatory molecules, thereby allowing the immune system to sustain the expression of molecules such as 4-1BB to a level commensurate with severity of infection.
|
pubmed:language |
eng
|
pubmed:journal | |
pubmed:citationSubset |
AIM
|
pubmed:chemical | |
pubmed:status |
MEDLINE
|
pubmed:month |
Jan
|
pubmed:issn |
1550-6606
|
pubmed:author | |
pubmed:issnType |
Electronic
|
pubmed:day |
15
|
pubmed:volume |
182
|
pubmed:owner |
NLM
|
pubmed:authorsComplete |
Y
|
pubmed:pagination |
934-47
|
pubmed:meshHeading |
pubmed-meshheading:19124736-4-1BB Ligand,
pubmed-meshheading:19124736-Administration, Intranasal,
pubmed-meshheading:19124736-Animals,
pubmed-meshheading:19124736-Antigens, CD137,
pubmed-meshheading:19124736-Epitopes, T-Lymphocyte,
pubmed-meshheading:19124736-Gene Expression Regulation,
pubmed-meshheading:19124736-Immunodominant Epitopes,
pubmed-meshheading:19124736-Influenza A Virus, H1N1 Subtype,
pubmed-meshheading:19124736-Influenza A Virus, H3N2 Subtype,
pubmed-meshheading:19124736-Mice,
pubmed-meshheading:19124736-Mice, Inbred C57BL,
pubmed-meshheading:19124736-Mice, Knockout,
pubmed-meshheading:19124736-Mice, Transgenic,
pubmed-meshheading:19124736-Orthomyxoviridae Infections,
pubmed-meshheading:19124736-Pneumonia, Viral,
pubmed-meshheading:19124736-Respiratory Function Tests,
pubmed-meshheading:19124736-Severity of Illness Index,
pubmed-meshheading:19124736-Virulence
|
pubmed:year |
2009
|
pubmed:articleTitle |
Endogenous 4-1BB ligand plays a critical role in protection from influenza-induced disease.
|
pubmed:affiliation |
Department of Immunology, University of Toronto, Toronto, Ontario, Canada.
|
pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, Non-U.S. Gov't
|