Statements in which the resource exists as a subject.
PredicateObject
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