Document Detail


Resistance of Crohn's disease T cells to multiple apoptotic signals is associated with a Bcl-2/Bax mucosal imbalance.
MedLine Citation:
PMID:  10395708     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
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:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Journal of immunology (Baltimore, Md. : 1950)     Volume:  163     ISSN:  0022-1767     ISO Abbreviation:  J. Immunol.     Publication Date:  1999 Jul 
Date Detail:
Created Date:  1999-07-29     Completed Date:  1999-07-29     Revised Date:  2013-05-24    
Medline Journal Info:
Nlm Unique ID:  2985117R     Medline TA:  J Immunol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1081-90     Citation Subset:  AIM; IM    
Affiliation:
Division of Gastroenterology, Molecular Cardiovascular Research Center, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA.
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MeSH Terms
Descriptor/Qualifier:
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:
DK30399/DK/NIDDK NIH HHS; DK50984/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
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

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