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NKT Cells from Normal and Tumor-Bearing Human Livers Are Phenotypically and Functionally Distinct from Murine NKT Cells

Tony Kenna, Lucy Golden Mason, Steven A. Porcelli, Yasuhiko Koezuka, John E. Hegarty, Cliona O’Farrelly and Derek G. Doherty
J Immunol August 15, 2003, 171 (4) 1775-1779; DOI: https://doi.org/10.4049/jimmunol.171.4.1775
Tony Kenna
*Education and Research Center and
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Lucy Golden Mason
*Education and Research Center and
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Steven A. Porcelli
‡ Department of Microbiology and Immunology, Albert Einstein College of Medicine, New York, NY 10461;
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Yasuhiko Koezuka
§ Pharmaceutical Research Laboratory, Kirin Brewery Co. Ltd., Gunma, Japan;
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John E. Hegarty
† Liver Unit, St. Vincent’s University Hospital, Dublin, Ireland;
¶ Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Ireland; and
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Cliona O’Farrelly
*Education and Research Center and
¶ Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Ireland; and
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Derek G. Doherty
∥ Institute of Immunology and Department of Biology, National University of Ireland, Maynooth, Ireland.
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  • FIGURE 1.
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    FIGURE 1.

    Small numbers of invariant Vα24Vβ11+ NKT cells accumulate in human liver. A, Representative flow cytometry dot plot showing Vα24 and Vβ11 TCR chain expression by gated CD3+ cells freshly isolated from blood and liver of a liver transplant donor. Numbers show percentages of CD3+ cells that express the Vα24Vβ11 TCR. B and C, Percentages of CD3+ cells in blood and liver of six liver transplant donors expressing Vα24 (B) and Vα24Vβ11 (C) TCR chains. Horizontal lines indicate medians. ∗, p = 0.02.

  • FIGURE 2.
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    FIGURE 2.

    Phenotypic characterization of human hepatic and peripheral blood Vα24+ T cells. A, Representative flow cytometry dot plot showing CD56, CD161, CD25, CD69, HLA-DR, and CD45RA expression by hepatic Vα24+ T cells from a liver transplant donor. B, Box plots showing median (horizontal lines), interquartile ranges (shaded areas), and ranges (error bars) of percentages of Vα24+ T cells in blood and liver of six liver transplant donors expressing CD4+, CD8+, and CD4−CD8− phenotypes, CD56, CD161, CD25, CD69, HLA-DR, and CD45RA. ∗, p = 0.03 for CD56, p = 0.02 for CD161, and p = 0.03 for CD69.

  • FIGURE 3.
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    FIGURE 3.

    Invariant NKT cells are selectively depleted in tumor-bearing liver. A, Box plots showing median (horizontal lines), interquartile ranges (shaded areas), and ranges (error bars) of percentages of CD3+ cells in normal donor and tumor-bearing liver expressing Vα24 TCR chain and Vα24Vβ11 TCR. ∗, p = 0.04. B, Box plots showing median, interquartile ranges, and ranges of percentages of hepatic Vα24+ T cells in six normal donor livers and nine tumor-bearing livers expressing CD4+, CD8+, and CD4−CD8− phenotypes, CD56, CD161, CD25, CD69, HLA-DR, and CD45RA. ∗, p = 0.05 for CD56, p = 0.03 for CD161, and p = 0.03 for HLA-DR.

  • FIGURE 4.
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    FIGURE 4.

    Hepatic NKT cells predominantly produce Th1 cytokines upon stimulation ex vivo. A, Representative flow cytometry dot plot showing IFN-γ, IL-2, TNF-α, and IL-4 expression by hepatic Vα24+ T cells stimulated for 4 h with PMA and ionomycin. The percentages of Vα24+ cells that express the cytokines are indicated in the upper right quadrants. B, Median percentages of Vα24+ cells in four normal donor livers and four tumor-bearing livers that express IFN-γ, IL-2, TNF-α, and IL-4 upon stimulation.

  • FIGURE 5.
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    FIGURE 5.

    HMC respond to αGalCer stimulation. Mean IFN-γ (A) and IL-4 (B) levels released by vehicle-, αGalCer-, and PHA-stimulated MNC isolated from blood and livers of five liver transplant donors and from three livers of patients with hepatic malignancy. IL-4 production by αGalCer-stimulated HMC was not detected using ELISA sensitive to 1 pg/ml. ND, PHA stimulation of tumor-bearing liver was not performed.

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The Journal of Immunology: 171 (4)
The Journal of Immunology
Vol. 171, Issue 4
15 Aug 2003
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NKT Cells from Normal and Tumor-Bearing Human Livers Are Phenotypically and Functionally Distinct from Murine NKT Cells
Tony Kenna, Lucy Golden Mason, Steven A. Porcelli, Yasuhiko Koezuka, John E. Hegarty, Cliona O’Farrelly, Derek G. Doherty
The Journal of Immunology August 15, 2003, 171 (4) 1775-1779; DOI: 10.4049/jimmunol.171.4.1775

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NKT Cells from Normal and Tumor-Bearing Human Livers Are Phenotypically and Functionally Distinct from Murine NKT Cells
Tony Kenna, Lucy Golden Mason, Steven A. Porcelli, Yasuhiko Koezuka, John E. Hegarty, Cliona O’Farrelly, Derek G. Doherty
The Journal of Immunology August 15, 2003, 171 (4) 1775-1779; DOI: 10.4049/jimmunol.171.4.1775
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