| Resistance of Crohn's disease T cells to multiple apoptotic signals is associated with a Bcl-2/Bax mucosal imbalance. | |
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MedLine Citation:
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PMID: 10395708 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Crohn's disease (CD) is a condition characterized by excessive numbers of activated T cells in the mucosa. We investigated whether a defect in apoptosis could prolong T cell survival and contribute to their accumulation in the mucosa. Apoptotic, Bcl-2+, and Bax+ cells in tissue sections were detected by the TUNEL method and immunohistochemistry. T cell apoptosis was induced by IL-2 deprivation, Fas Ag ligation, and exposure to TNF-alpha and nitric oxide. TUNEL+ leukocytes were few in control, CD, and ulcerative colitis (UC) mucosa, with occasional CD68+ and myeloperoxidase+, but no CD45RO+, apoptotic cells. Compared with control and UC, CD T cells grew remarkably more in response to IL-2 and were significantly more resistant to IL-2 deprivation-induced apoptosis. CD T cells were also more resistant to Fas- and nitric oxide-mediated apoptosis, whereas TNF-alpha failed to induce cell death in all groups. Compared with control, CD mucosa contained similar numbers of Bcl-2+, but fewer Bax+, cells, while UC mucosa contained fewer Bcl-2+, but more Bax+, cells. Hence, the Bcl-2/Bax ratio was significantly higher in CD and lower in UC. These results indicate that CD may represent a disorder where the rate of T cell proliferation exceeds that of cell death. Insufficient T cell apoptosis may interfere with clonal deletion and maintenance of tolerance, and result in inappropriate T cell accumulation contributing to chronic inflammation. |
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Authors:
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K Ina; J Itoh; K Fukushima; K Kusugami; T Yamaguchi; K Kyokane; A Imada; D G Binion; A Musso; G A West; G M Dobrea; T S McCormick; E G Lapetina; A D Levine; C A Ottaway; C Fiocchi |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Journal of immunology (Baltimore, Md. : 1950) Volume: 163 ISSN: 0022-1767 ISO Abbreviation: J. Immunol. Publication Date: 1999 Jul |
Date Detail:
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Created Date: 1999-07-29 Completed Date: 1999-07-29 Revised Date: 2013-05-24 |
Medline Journal Info:
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Nlm Unique ID: 2985117R Medline TA: J Immunol Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 1081-90 Citation Subset: AIM; IM |
Affiliation:
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Division of Gastroenterology, Molecular Cardiovascular Research Center, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Adolescent Adult Aged Aged, 80 and over Antigens, CD Antigens, CD28 / physiology Antigens, CD80 / physiology Antigens, CD95 / physiology Antigens, Differentiation / physiology Apoptosis / immunology* CTLA-4 Antigen Cell Division / immunology Cell Line Child Crohn Disease / immunology*, pathology Culture Media Female Humans Immunity, Innate Immunoconjugates* Immunophenotyping Interleukin-10 / pharmacology Interleukin-2 / biosynthesis, deficiency Intestinal Mucosa / immunology*, metabolism, pathology Lymphocyte Activation Lymphocyte Count Male Middle Aged Nitric Oxide / physiology Proto-Oncogene Proteins / biosynthesis, immunology* Proto-Oncogene Proteins c-bcl-2 / biosynthesis, immunology* T-Lymphocyte Subsets / immunology*, metabolism, pathology Tumor Necrosis Factor-alpha / physiology bcl-2-Associated X Protein |
| Grant Support | |
ID/Acronym/Agency:
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DK30399/DK/NIDDK NIH HHS; DK50984/DK/NIDDK NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Antigens, CD; 0/Antigens, CD28; 0/Antigens, CD80; 0/Antigens, CD95; 0/Antigens, Differentiation; 0/BAX protein, human; 0/CTLA-4 Antigen; 0/CTLA4 protein, human; 0/Culture Media; 0/Immunoconjugates; 0/Interleukin-2; 0/Proto-Oncogene Proteins; 0/Proto-Oncogene Proteins c-bcl-2; 0/Tumor Necrosis Factor-alpha; 0/bcl-2-Associated X Protein; 10102-43-9/Nitric Oxide; 130068-27-8/Interleukin-10; 7D0YB67S97/abatacept |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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