Invariant NKT cells and CD1d(+) cells amass in human omentum and are depleted in patients with cancer and obesity.
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.
Lynch
Lydia
L
Education and Research Centre, St.Vincent's University Hospital, Dublin, Ireland. llynch1@bidmc.harvard.edu
O'Shea
Donal
D
Winter
Desmond C
DC
Geoghegan
Justin
J
Doherty
Derek G
DG
O'Farrelly
Cliona
C
D017252:CD3 Complex / Q000276:immunology; D056970:Co-Repressor Proteins; D005260:Female; D005434:Flow Cytometry; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D007371:Interferon-gamma / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D017493:Leukocyte Common Antigens / Q000276:immunology; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D055611:Natural Killer T-Cells / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D009369:Neoplasms / Q000276:immunology* / Q000473:pathology; D009765:Obesity / Q000276:immunology* / Q000473:pathology; D009852:Omentum / Q000276:immunology* / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology
C117400:C1D protein, human; D017252:CD3 Complex; D056970:Co-Repressor Proteins; D012333:RNA, Messenger; D016693:Receptors, Antigen, T-Cell, alpha-beta; D012097:Repressor Proteins; D015847:Interleukin-4; D007371:Interferon-gamma; D017493:Leukocyte Common Antigens; C516769:PTPRC protein, human