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The Human Liver Contains Multiple Populations of NK Cells, T Cells, and CD3+CD56+ Natural T Cells with Distinct Cytotoxic Activities and Th1, Th2, and Th0 Cytokine Secretion Patterns
Open accessAbstract
The human liver contains significant numbers of T cells, NK cells, and lymphocytes that coexpress T and NK cell receptors. To evaluate their functional activities, we have compared the cytotoxic activities and cytokines produced by normal adult hepatic CD3+CD56− (T) cells, CD3−CD56+ (NK) cells, and CD3+CD56+ (natural T (NT)) cells. In cytotoxicity assays using immunomagnetic bead-purified NK cell, T cell, and NT cell subpopulations as effectors, fresh hepatic NK cells lysed K562 targets, while NT cells could be induced to do so by culturing with IL-2. Both NT and T cells were capable of redirected cytolysis of P815 cells using Abs to CD3. Flow cytometric analysis of cytokine production by fresh hepatic lymphocyte subsets activated by CD3 cross-linking or PMA and ionomycin stimulation indicated that NT cells and T cells could produce IFN-γ, TNF-α, IL-2, and/or IL-4, but little or no IL-5, while NK cells produced IFN-γ and/or TNF-α only. The majority of NT cells produced inflammatory (Th1) cytokines only; however, ∼6% of all hepatic T cells, which included 5% of Vα24 TCR-bearing NT cells and 2% of γδTCR+ cells, simultaneously produced IFN-γ and IL-4. The existence of such large numbers of cytotoxic lymphocytes with multiple effector functions suggests that the liver is an important site of innate immune responses, early regulation of adaptive immunity, and possibly peripheral deletion of autologous cells.
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“NKs represent the largest population of lymphocytes in the liver(72, 73).”
From The liver as a central "hub" of the immune system: pathophysiological implications (2025) · cites this paper as [73]
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Metadata
- Authors
- Doherty, D. G., Norris, S., Madrigal-Estebas, L., McEntee, G., Traynor, O., Hegarty, J. E., & O’Farrelly, C.
- Affiliations
- University College Dublin (IE)
- St. Vincent's University Hospital (IE)
- Corresponding author
- Norris, Suzanne
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 1999-08
- Volume
- 163
- Issue
- 4
- Pages
- 2314-2321
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W2139250003
- Cited by
- 350
- References
- 53
- Citations by year
- 2026: 2 · 2025: 6 · 2024: 6 · 2023: 9 · 2022: 7 · 2021: 15 · 2020: 8 · 2019: 6 · 2018: 8 · 2017: 10 · 2016: 11 · 2015: 11 · 2014: 8 · 2013: 11 · 2012: 7
- FWCI
- 6.95
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Immunology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immune Cell Function and Interaction
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Immunology and Microbiology › Immunology › Reproductive System and Pregnancy
- Keywords
- hepatic lymphocytes, natural killer cells, T cells, CD3+CD56+ cells, cytotoxicity, cytokine production, Th1 cytokines, Th2 cytokines, interleukin-2, interferon-gamma, TNF-α, IL-4, γδ T cells, innate immunity, liver
- MeSH terms
- Adult, Cell Separation, Cells, Cultured, Cytotoxicity, Immunologic, Humans, Killer Cells, Natural, Liver, Receptors, Antigen, T-Cell, T-Lymphocytes, Cytotoxic, Killer Cells, Lymphokine-Activated, Lymphocyte Subsets, Cytokines, CD3 Complex, Th1 Cells, Th2 Cells, CD56 Antigen
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