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

Invariant NKT cells and CD1d + cells amass in human omentum and are depleted in patients with... 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 Vα24Jα18 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‐γ 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. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png European Journal of Immunology Wiley

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

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Publisher
Wiley
Copyright
Copyright © 2009 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim
ISSN
0014-2980
eISSN
1521-4141
DOI
10.1002/eji.200939349
pmid
19585513
Publisher site
See Article on Publisher Site

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 Vα24Jα18 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‐γ 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.

Journal

European Journal of ImmunologyWiley

Published: Jul 1, 2009

References

  • CD1: antigen presentation and T cell function
    Brigl, Brigl; Brenner, Brenner
  • The biology of NKT cells
    Bendelac, Bendelac; Savage, Savage; Teyton, Teyton
  • The ins and outs of CD1 molecules: bringing lipids under immunological surveillance
    Gumperz, Gumperz
  • Functionally distinct subsets of CD1d‐restricted natural killer T cells revealed by CD1d tetramer staining
    Gumperz, Gumperz; Miyake, Miyake; Yamamura, Yamamura; Brenner, Brenner
  • Cellular subsets of the milky spots in the human greater omentum
    Shimotsuma, Shimotsuma; Takahashi, Takahashi; Kawata, Kawata; Dux, Dux
  • Activated omentum becomes rich in factors that promote healing and tissue regeneration
    Litbarg, Litbarg; Gudehithlu, Gudehithlu; Sethupathi, Sethupathi; Arruda, Arruda; Dunea, Dunea; Singh, Singh
  • Diverse populations of T cells with NK cell receptors accumulate in the human intestine in health and in colorectal cancer
    O'Keeffe, O'Keeffe; Doherty, Doherty; Kenna, Kenna; Sheahan, Sheahan; O'Donoghue, O'Donoghue; Hyland, Hyland; O'Farrelly, O'Farrelly
  • A reversible defect in natural killer T cell function characterizes the progression of premalignant to malignant multiple myeloma
    Dhodapkar, Dhodapkar; Geller, Geller; Chang, Chang; Shimizu, Shimizu; Fujii, Fujii; Dhodapkar, Dhodapkar; Krasovsky, Krasovsky

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