| Interleukin 21 up-regulates perforin-mediated cytotoxic activity of human intra-epithelial lymphocytes. | |
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MedLine Citation:
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PMID: 19489126 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Human intra-epithelial lymphocytes (IELs) are predominantly T-cell receptor-alphabeta(+) (TCR-alphabeta(+)) CD8(+) CD45RO(+) memory T cells located between intestinal epithelial cells. They respond to a greater extent to stimulation with interleukin (IL)-15 than to CD3/TCR triggering, suggesting that they react to the cytokine milieu in their local environment rather than to cognate antigen. A newly described member of the gammac cytokine family, IL-21, has potent antitumor effects. As IELs resemble lymphocytes infiltrating neoplastic lesions, their response to IL-21 may be relevant in vivo. Here, IL-21 was shown to increase perforin-mediated cytotoxicity and serine esterase release by IELs. This IL-21-mediated up-regulation occurred without changes in IEL survival or cell division. Interestingly, the effects of IL-21 occurred without increased phosphorylation of signal transducer and activator of transcription (STAT)1, STAT3, STAT4, STAT5, extracellular signal-regulated kinase (ERK), or p38. IL-21 had no effect on Fas ligand (FL)- or tumour necrosis factor-alpha (TNF-alpha)-mediated cytotoxicity, but it down-regulated IL-15-stimulated expression of CD25 and CD94, indicating that it has both positive and negative actions. This functional profile is unique to human IELs, emphasizing that they are a distinct compartment of lymphocytes and that IL-21 may promote their role in tumour immunosurveillance. |
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Authors:
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Ellen C Ebert |
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Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: Immunology Volume: 127 ISSN: 1365-2567 ISO Abbreviation: Immunology Publication Date: 2009 Jun |
Date Detail:
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Created Date: 2009-06-01 Completed Date: 2009-07-31 Revised Date: 2010-09-24 |
Medline Journal Info:
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Nlm Unique ID: 0374672 Medline TA: Immunology Country: England |
Other Details:
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Languages: eng Pagination: 206-15 Citation Subset: IM |
Affiliation:
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UMDNJ-Robert Wood Johnson Medical School, New Brunswick, NJ, USA. ebertec@umdnj.edu |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Cell Proliferation Cell Survival / immunology Cells, Cultured Cytoplasmic Granules / immunology Cytotoxicity, Immunologic / immunology Epithelial Cells / immunology Fas Ligand Protein / immunology Humans Immunity, Mucosal Interleukin-15 / immunology Interleukins / immunology* Intestinal Mucosa / immunology* Jejunum / immunology Perforin / immunology* Phosphorylation / immunology STAT Transcription Factors / immunology Tumor Necrosis Factor-alpha / immunology Up-Regulation / immunology |
| Chemical | |
Reg. No./Substance:
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0/Fas Ligand Protein; 0/Interleukin-15; 0/Interleukins; 0/STAT Transcription Factors; 0/Tumor Necrosis Factor-alpha; 0/interleukin-21; 126465-35-8/Perforin |
| Comments/Corrections | |
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