NKT cells from normal and tumor-bearing human livers are phenotypically and functionally distinct from murine NKT cells

Kenna, Tony, Golden-Mason, Lucy, Porcelli, Steven A., Koezuka, Yasuhiko, Hegarty, John E., O'Farrelly, Cliona, & Doherty, Derek G. (2003) NKT cells from normal and tumor-bearing human livers are phenotypically and functionally distinct from murine NKT cells. Journal of Immunology, 171(4), pp. 1775-1779.

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Abstract

A major group of murine NK T (NKT) cells express an invariant Vα14Jα18 TCR α-chain specific for glycolipid Ags presented by CD1d. Murine Vα14Jα18+ account for 30–50% of hepatic T cells and have potent antitumor activities. We have enumerated and characterized their human counterparts, Vα24Vβ11+ 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 Vα24+ NKT cells express the Vβ11 chain. They include CD4+, CD8+, and CD4−CD8− cells, and many express the NK cell markers CD56, CD161, and/or CD69. Importantly, human hepatic Vα24+ T cells are potent producers of IFN-γ and TNF-α, but not IL-2 or IL-4, when stimulated pharmacologically or with the NKT cell ligand, α-galactosylceramide. Vα24+Vβ11+ 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-γ in response to α-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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ID Code: 94061
Item Type: Journal Article
Refereed: Yes
Additional URLs:
Keywords: Animals, Cell Differentiation/immunology, Cell Division/immunology, Cytokines/biosynthesis, Galactosylceramides/pharmacology, Humans, Immunophenotyping, Interferon-gamma/biosynthesis, Interleukin-4/biosynthesis, Killer Cells, Natural/cytology/ immunology/metabolism/pathology, Liver/cytology/ immunology/metabolism, Liver Neoplasms/ immunology/metabolism/pathology, Lymphopenia/immunology/pathology, Mice, Protein Isoforms/biosynthesis, Receptors, Antigen, T-Cell, alpha-beta/biosynthesis, T-Lymphocyte Subsets/cytology/ immunology/metabolism/pathology, Th1 Cells/immunology/metabolism, Tumor Cells, Cultured
DOI: 10.4049/jimmunol.171.4.1775
ISSN: 1550-6606
Divisions: Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
Copyright Owner: Copyright 2003 by The American Association of Immunologists
Deposited On: 22 Mar 2016 23:03
Last Modified: 23 Mar 2016 00:16

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