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

Lydia Lynch, Donal O'Shea, Desmond C. Winter, Justin Geoghegan, Derek G. Doherty, Cliona O'Farrelly

Research output: Contribution to journalArticlepeer-review

216 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1893-1901
Number of pages9
JournalEuropean Journal of Immunology
Volume39
Issue number7
DOIs
StatePublished - 2009
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Keywords

  • CD1d
  • Human
  • NKT cells
  • Obesity
  • Tumor immunity

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