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* Education and Research Center and
Liver Unit, St. Vincent’s University Hospital, Dublin, Ireland;
Department of Microbiology and Immunology, Albert Einstein College of Medicine, New York, NY 10461;
Pharmaceutical Research Laboratory, Kirin Brewery Co. Ltd., Gunma, Japan;
¶
Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Ireland; and
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Institute of Immunology and Department of Biology, National University of Ireland, Maynooth, Ireland.
A major group of murine NK T (NKT) cells express an invariant V
14J18 TCR -chain specific for glycolipid Ags presented by CD1d. Murine V14J18+ account for 30–50% of hepatic T cells and have potent antitumor activities. We have enumerated and characterized their human counterparts, V24V
11+ NKT cells, freshly isolated from histologically normal and tumor-bearing livers. In contrast to mice, human NKT cells are found in small numbers in healthy liver (0.5% of CD3+ cells) and blood (0.02%). In contrast to those in blood, most hepatic V24+ NKT cells express the V11 chain. They include CD4+, CD8+, and CD4-CD8- cells, and many express the NK cell markers CD56, CD161, and/or CD69. Importantly, human hepatic V24+ T cells are potent producers of IFN-
and TNF-, but not IL-2 or IL-4, when stimulated pharmacologically or with the NKT cell ligand, -galactosylceramide. V24+V11+ cell numbers are reduced in tumor-bearing compared with healthy liver (0.1 vs 0.5%; p < 0.04). However, hepatic cells from cancer patients and healthy donors release similar amounts of IFN- in response to -galactosylceramide. These data indicate that hepatic NKT cell repertoires are phenotypically and functionally distinct in humans and mice. Depletions of hepatic NKT cell subpopulations may underlie the susceptibility to metastatic liver disease.
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