Invariant NKT cells and CD1d(+) cells amass in human omentum and are depleted in patients with cancer and obesity.

Hdl Handle:
http://hdl.handle.net/10147/207531
Title:
Invariant NKT cells and CD1d(+) cells amass in human omentum and are depleted in patients with cancer and obesity.
Authors:
Lynch, Lydia; O'Shea, Donal; Winter, Desmond C; Geoghegan, Justin; Doherty, Derek G; O'Farrelly, Cliona
Affiliation:
Education and Research Centre, St.Vincent's University Hospital, Dublin, Ireland., llynch1@bidmc.harvard.edu
Citation:
Eur J Immunol. 2009 Jul;39(7):1893-901.
Journal:
European journal of immunology
Issue Date:
1-Feb-2012
URI:
http://hdl.handle.net/10147/207531
DOI:
10.1002/eji.200939349
PubMed ID:
19585513
Abstract:
Invariant NKT (iNKT) cells recognize lipid antigens presented by CD1d and respond rapidly by killing tumor cells and release cytokines that activate and regulate adaptive immune responses. They are essential for tumor rejection in various mouse models, but clinical trials in humans involving iNKT cells have been less successful, partly due to their rarity in humans compared with mice. Here we describe an accumulation of functional iNKT cells in human omentum, a migratory organ with healing properties. Analysis of 39 omental samples revealed that T cells are the predominant lymphoid cell type and of these, 10% expressed the invariant Valpha24Jalpha18 TCR chain, found on iNKT cells, higher than in any other human organ tested to date. About 15% of omental hematopoietic cells expressed CD1d, compared with 1% in blood (p<0.001). Enriched omental iNKT cells killed CD1d(+) targets and released IFN-gamma and IL-4 upon activation. Omental iNKT-cell frequencies were lower in patients with severe obesity (p=0.005), and with colorectal carcinoma (p=0.004) compared with lean healthy subjects. These data suggest a novel role for the omentum in immune regulation and tumor immunity and identify it as a potential source of iNKT cells for therapeutic use.
Language:
eng
MeSH:
Antigens, CD3/immunology; Antigens, CD45/immunology; Co-Repressor Proteins; Female; Flow Cytometry; Gene Expression; Humans; Immunohistochemistry; Interferon-gamma/metabolism; Interleukin-4/metabolism; Lymphocyte Count; Male; Middle Aged; Natural Killer T-Cells/*immunology/metabolism/pathology; Neoplasms/*immunology/pathology; Obesity/*immunology/pathology; Omentum/*immunology/pathology; RNA, Messenger/genetics/metabolism; Receptors, Antigen, T-Cell, alpha-beta/metabolism; Repressor Proteins/genetics/*immunology; Reverse Transcriptase Polymerase Chain Reaction; T-Lymphocytes/immunology/metabolism/pathology
ISSN:
1521-4141 (Electronic); 0014-2980 (Linking)

Full metadata record

DC FieldValue Language
dc.contributor.authorLynch, Lydiaen_GB
dc.contributor.authorO'Shea, Donalen_GB
dc.contributor.authorWinter, Desmond Cen_GB
dc.contributor.authorGeoghegan, Justinen_GB
dc.contributor.authorDoherty, Derek Gen_GB
dc.contributor.authorO'Farrelly, Clionaen_GB
dc.date.accessioned2012-02-01T10:30:27Z-
dc.date.available2012-02-01T10:30:27Z-
dc.date.issued2012-02-01T10:30:27Z-
dc.identifier.citationEur J Immunol. 2009 Jul;39(7):1893-901.en_GB
dc.identifier.issn1521-4141 (Electronic)en_GB
dc.identifier.issn0014-2980 (Linking)en_GB
dc.identifier.pmid19585513en_GB
dc.identifier.doi10.1002/eji.200939349en_GB
dc.identifier.urihttp://hdl.handle.net/10147/207531-
dc.description.abstractInvariant NKT (iNKT) cells recognize lipid antigens presented by CD1d and respond rapidly by killing tumor cells and release cytokines that activate and regulate adaptive immune responses. They are essential for tumor rejection in various mouse models, but clinical trials in humans involving iNKT cells have been less successful, partly due to their rarity in humans compared with mice. Here we describe an accumulation of functional iNKT cells in human omentum, a migratory organ with healing properties. Analysis of 39 omental samples revealed that T cells are the predominant lymphoid cell type and of these, 10% expressed the invariant Valpha24Jalpha18 TCR chain, found on iNKT cells, higher than in any other human organ tested to date. About 15% of omental hematopoietic cells expressed CD1d, compared with 1% in blood (p<0.001). Enriched omental iNKT cells killed CD1d(+) targets and released IFN-gamma and IL-4 upon activation. Omental iNKT-cell frequencies were lower in patients with severe obesity (p=0.005), and with colorectal carcinoma (p=0.004) compared with lean healthy subjects. These data suggest a novel role for the omentum in immune regulation and tumor immunity and identify it as a potential source of iNKT cells for therapeutic use.en_GB
dc.language.isoengen_GB
dc.subject.meshAntigens, CD3/immunologyen_GB
dc.subject.meshAntigens, CD45/immunologyen_GB
dc.subject.meshCo-Repressor Proteinsen_GB
dc.subject.meshFemaleen_GB
dc.subject.meshFlow Cytometryen_GB
dc.subject.meshGene Expressionen_GB
dc.subject.meshHumansen_GB
dc.subject.meshImmunohistochemistryen_GB
dc.subject.meshInterferon-gamma/metabolismen_GB
dc.subject.meshInterleukin-4/metabolismen_GB
dc.subject.meshLymphocyte Counten_GB
dc.subject.meshMaleen_GB
dc.subject.meshMiddle Ageden_GB
dc.subject.meshNatural Killer T-Cells/*immunology/metabolism/pathologyen_GB
dc.subject.meshNeoplasms/*immunology/pathologyen_GB
dc.subject.meshObesity/*immunology/pathologyen_GB
dc.subject.meshOmentum/*immunology/pathologyen_GB
dc.subject.meshRNA, Messenger/genetics/metabolismen_GB
dc.subject.meshReceptors, Antigen, T-Cell, alpha-beta/metabolismen_GB
dc.subject.meshRepressor Proteins/genetics/*immunologyen_GB
dc.subject.meshReverse Transcriptase Polymerase Chain Reactionen_GB
dc.subject.meshT-Lymphocytes/immunology/metabolism/pathologyen_GB
dc.titleInvariant NKT cells and CD1d(+) cells amass in human omentum and are depleted in patients with cancer and obesity.en_GB
dc.contributor.departmentEducation and Research Centre, St.Vincent's University Hospital, Dublin, Ireland., llynch1@bidmc.harvard.eduen_GB
dc.identifier.journalEuropean journal of immunologyen_GB
dc.description.provinceLeinster-

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