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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2008-3-31
pubmed:abstractText
OX40, a member of the tumor necrosis factor receptor (TNF-R) superfamily, has been shown to play an important role in the survival of antigen-specific CD4(+) T cells. We have previously reported that stimulation of the OX40-expressing and HIV-1 chronically infected T cell line, ACH-2/OX40, with either OX40 ligand (OX40L)-expressing cells or with TNF resulted in the activation of HIV-1 followed by apoptotic cell death. In the present study we found that costimulation via OX40 and TNF-R in OX40-expressing HIV-1-infected T cell lines leads to a marked reduction of HIV-1 production associated with rapid cell death. Since HIV-1-negative OX40(+) T cell lines underwent rapid apoptotic cell death after OX40L and TNF stimulation, it was reasoned that the ACH-2/OX40 cell death was unlikely to be due to HIV-1 infection. Furthermore, we found that the OX40-mediated apoptosis of the CD4(+) T cell line, Molt-4/CCR5-OX40 (M/R5-OX40), required (1) signals mediated via the cytoplasmic tail of OX40, (2) activation of the caspase cascade, including caspase-8 and caspase-3, and (3) induction of endogenous TNF-alpha, but not of TNF-beta, FasL, or TNF-related apoptosis-inducing ligand (TRAIL), suggesting that this apoptosis occurred indirectly via the TNF/TNF-R system. Finally, a fraction of primary activated CD4(+) T cells, expressing high levels of OX40, underwent apoptosis, as revealed by annexin V staining, after cocultivation with OX40L(+) cells. These results suggest a new biological role of the OX40L/OX40 system in controlling the fate of activated CD4(+) T cells and of controlling HIV-1 infection in inflammatory environments.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0889-2229
pubmed:author
pubmed:issnType
Print
pubmed:volume
24
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
423-35
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
Enhancement of OX40-induced apoptosis by TNF coactivation in OX40-expressing T cell lines in vitro leading to decreased targets for HIV type 1 production.
pubmed:affiliation
Department of Immunology, Graduate School of Medicine, University of the Ryukyus, Nishihara, Okinawa 903-0215, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't