Source:http://linkedlifedata.com/resource/pubmed/id/21215812
Switch to
| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
6
|
| pubmed:dateCreated |
2011-5-23
|
| pubmed:abstractText |
T cell responses to allogeneic targets arise predominantly from the naïve pool. However, in humans, the risk of graft-versus-host disease is increased if the donor has circulating T cells recognizing multiple persistent DNA viruses, suggesting that memory T cells also contribute to the alloresponse. To examine HLA alloreactivity, we used flow cytometry-based proliferation and cytokine production assays. We identified the clonal identity of virus-specific T cells cross-reacting with HLA-disparate targets by sequencing the T cell receptor ? chains in virus-specific T cell lines restimulated with cognate and HLA-disparate targets and sorting these chains according to cytokine response. We confirmed that naïve T cells from cord blood and adult individuals responded to HLA-mismatched target cells. In addition, in adults, we identified memory T cells responding by cytokine release to HLA-mismatched targets both in direct assays and after 8 days of culture with allogeneic stimulator cells. Epstein-Barr virus-specific and cytomegalovirus-specific T cells, tested against a panel of 30 T cell antigen-presenting cells with a broad coverage of the most prominent HLA types, displayed specificity for certain mismatched HLA alleles. Sequencing of the T cell receptor ? chain demonstrated a clonotypic identity of cells that responded to both viral and allogeneic stimulation. These findings show conclusively that alloresponses in humans are not confined to the naïve T cell subset, and that memory viral antigen-specific T cells can cross-react with specific mismatched HLA-peptide complexes not presenting with cytomegalovirus or Epstein-Barr virus peptides.
|
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical | |
| pubmed:status |
MEDLINE
|
| pubmed:month |
Jun
|
| pubmed:issn |
1523-6536
|
| pubmed:author |
pubmed-author:AmbrozakDavid RDR,
pubmed-author:BarrettA JohnAJ,
pubmed-author:DouekDaniel CDC,
pubmed-author:HenselNancy FNF,
pubmed-author:KeyvanfarKeyvanK,
pubmed-author:McCoyJ PhilipJPJr,
pubmed-author:MelenhorstJ JosephJJ,
pubmed-author:ScheinbergPhillipP,
pubmed-author:SmithMelodyM,
pubmed-author:WilliamsAnnA
|
| pubmed:copyrightInfo |
Published by Elsevier Inc.
|
| pubmed:issnType |
Electronic
|
| pubmed:volume |
17
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
800-9
|
| pubmed:meshHeading |
pubmed-meshheading:21215812-Adult,
pubmed-meshheading:21215812-Antigen-Presenting Cells,
pubmed-meshheading:21215812-Antigens, Viral,
pubmed-meshheading:21215812-CD8-Positive T-Lymphocytes,
pubmed-meshheading:21215812-Cross Reactions,
pubmed-meshheading:21215812-Cytokines,
pubmed-meshheading:21215812-Cytomegalovirus,
pubmed-meshheading:21215812-Female,
pubmed-meshheading:21215812-Fetal Blood,
pubmed-meshheading:21215812-Flow Cytometry,
pubmed-meshheading:21215812-Graft vs Host Disease,
pubmed-meshheading:21215812-HLA Antigens,
pubmed-meshheading:21215812-Herpesvirus 4, Human,
pubmed-meshheading:21215812-Humans,
pubmed-meshheading:21215812-Immunologic Memory,
pubmed-meshheading:21215812-Pregnancy,
pubmed-meshheading:21215812-Receptors, Antigen, T-Cell, alpha-beta,
pubmed-meshheading:21215812-Sequence Analysis, DNA
|
| pubmed:year |
2011
|
| pubmed:articleTitle |
Alloreactivity across HLA barriers is mediated by both naïve and antigen-experienced T cells.
|
| pubmed:affiliation |
Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892-1202, USA. melenhoj@nhlbi.nih.gov
|
| pubmed:publicationType |
Journal Article,
Research Support, N.I.H., Intramural
|