Linked Life Data

7689606

Source:http://linkedlifedata.com/resource/pubmed/id/7689606

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
1993-9-28
pubmed:abstractText
Integrin ligands intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) can efficiently costimulate proliferation of resting T cells but not that of Ag-specific T cells. In contrast, CD28 ligand B7 and CD2 ligand leukocyte function-associated Ag (LFA-3) can support IL-2 synthesis and proliferation of Ag-specific T cells more efficiently than that of resting T cells. The molecular basis for this differential costimulation of T cells is poorly understood. In this study, using mAb and soluble IgC gamma 1 chimeras of these adhesion molecules, we demonstrate that coligation of the TCR and CD11a/CD18 (LFA-1/beta 2 integrin) or CD29/CD49d (very late activation Ag-4/beta 1 integrin) using anti-TCR mAb and either ICAM-1 or VCAM-1 induces activation-dependent death of DRw6-specific CD4+ T cells. Similar coligation of the TCR with CD2 or CD28 using either mAb or ligands LFA-3 or B7 not only lacked the ability to induce death but also failed to reverse or inhibit integrin-facilitated death of DRw6-specific T cells. Each of these ligands augmented anti-TCR mAb-induced transcription of IL-2 and IL-4 genes. Exogenous addition of IL-2 and IL-4 did not reverse the integrin-supported T cell death. The death-promoting costimulatory effects of ICAM-1 and VCAM-1 were observed with Ag-specific chronically stimulated T cells but not with either resting T cells or those activated in short-term cultures. Treatment of T cells with cyclosporin A or a protein tyrosine kinase inhibitor herbimycin A inhibited ICAM-1 or VCAM-1-promoted activation-induced T cell death. The Ag-specific T cells that survived death-promoting effects of ICAM-1 or VCAM-1 proliferated efficiently upon restimulation with these ligands. Exposure of DRw6-specific T cells to DRw6+ B7+ ICAM-1+ LFA-3+ VCAM-1+ APC but not DR3+ B7+ ICAM-1+ LFA-3+ VCAM-1+ APC induced death of these T cells. This effect was blocked by pretreatment of T cells with mAb directed at CD18 or CD29 but not with those against CD2 or CD28. Taken together, these results suggest that TCR-directed engagement of integrins by their ligands ICAM-1 or VCAM-1 induces activation-dependent death of some perhaps more differentiated Ag-specific T cells and this may be an important homeostatic mechanism by which functional expression of Ag-specific T cells is regulated during an ongoing immune response.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0022-1767
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
151
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2368-79
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:7689606-Antigen-Presenting Cells, pubmed-meshheading:7689606-Base Sequence, pubmed-meshheading:7689606-Benzoquinones, pubmed-meshheading:7689606-CD4-Positive T-Lymphocytes, pubmed-meshheading:7689606-Cell Adhesion Molecules, pubmed-meshheading:7689606-Cell Death, pubmed-meshheading:7689606-Cell Line, pubmed-meshheading:7689606-Cells, Cultured, pubmed-meshheading:7689606-Cyclosporine, pubmed-meshheading:7689606-Humans, pubmed-meshheading:7689606-Intercellular Adhesion Molecule-1, pubmed-meshheading:7689606-Interleukins, pubmed-meshheading:7689606-Lactams, Macrocyclic, pubmed-meshheading:7689606-Lymphocyte Activation, pubmed-meshheading:7689606-Molecular Sequence Data, pubmed-meshheading:7689606-Quinones, pubmed-meshheading:7689606-Receptors, Antigen, T-Cell, pubmed-meshheading:7689606-Vascular Cell Adhesion Molecule-1
pubmed:year
1993
pubmed:articleTitle
Costimulation with integrin ligands intercellular adhesion molecule-1 or vascular cell adhesion molecule-1 augments activation-induced death of antigen-specific CD4+ T lymphocytes.
pubmed:affiliation
Bristol-Myers Squibb Pharmaceutical Research Institute, Seattle, WA 98121.
pubmed:publicationType
Journal Article