| In vivo apoptosis of diabetogenic T cells in NOD mice by IFN-gamma/TNF-alpha. | |
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MedLine Citation:
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PMID: 15492021 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Immunization with mycobacterial preparation such as Bacille Calmette-Guerin (BCG) or complete Freund's adjuvant (CFA) prevents the onset and recurrence of type 1 diabetes in non-obese diabetic (NOD) mice. In this study, we explored the mechanism underlying the down-regulation of diabetogenic T cells by BCG treatment. We found that the potential of splenocytes from BCG-immunized diabetic NOD mice to adoptively transfer diabetes was significantly impaired. BCG immunization sequentially induced the production of TNF-alpha, IFN-gamma and IL-4 by splenocytes, increased the expression of Fas(high) (Apo-1/CD95), Fas ligand (FasL, CD95L) and TNF receptor (TNFR) on T cells leading to T cell apoptosis. The primary role of IFN-gamma and TNF-alpha in BCG-immunotherapy was demonstrated by (i) reversing the immune regulatory effect of BCG by in vivo treatment with neutralizing anti-cytokine antibodies, (ii) inducing effect similar to BCG by treatment with these cytokines. We show that Fas and TNF are two pathways in BCG-induced apoptosis of diabetogenic T cells, since in vitro blocking FasL or TNFR1 with antibody reduced T cell apoptosis and increased T cell proliferative response. In addition, TNF-alpha and agonistic anti-Fas antibody had a synergistic effect on the in vitro apoptosis of diabetogenic T cells. Our results suggest that BCG down-regulates destructive autoimmunity by TNF-alpha/IFN-gamma-induced apoptosis of diabetogenic T cells through both Fas and TNF pathways. These studies provide a novel mechanism for blocking disease recurrence and immune modulating effect of BCG immunization in type 1 diabetes. |
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Authors:
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Hui-Yu Qin; Pratibha Chaturvedi; Bhagirath Singh |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2004-10-18 |
Journal Detail:
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Title: International immunology Volume: 16 ISSN: 0953-8178 ISO Abbreviation: Int. Immunol. Publication Date: 2004 Dec |
Date Detail:
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Created Date: 2004-11-16 Completed Date: 2005-04-18 Revised Date: 2008-11-21 |
Medline Journal Info:
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Nlm Unique ID: 8916182 Medline TA: Int Immunol Country: England |
Other Details:
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Languages: eng Pagination: 1723-32 Citation Subset: IM |
Affiliation:
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Department of Microbiology and Immunology, University of Western Ontario, Canada. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Antigens, CD95 / metabolism Apoptosis* Autoimmunity Diabetes Mellitus, Type 1 / immunology*, therapy Fas Ligand Protein Immunization Immunotherapy, Active Interferon-gamma / pharmacology, physiology* Interleukin-4 / pharmacology, physiology Membrane Glycoproteins / metabolism Mice Mice, Inbred NOD Mycobacterium bovis / immunology* Receptors, Tumor Necrosis Factor, Type I / metabolism Recurrence / prevention & control Spleen / cytology, immunology T-Lymphocytes / drug effects, immunology* Tumor Necrosis Factor-alpha / pharmacology, physiology* |
| Chemical | |
Reg. No./Substance:
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0/Antigens, CD95; 0/Fas Ligand Protein; 0/Fasl protein, mouse; 0/Membrane Glycoproteins; 0/Receptors, Tumor Necrosis Factor, Type I; 0/Tumor Necrosis Factor-alpha; 207137-56-2/Interleukin-4; 82115-62-6/Interferon-gamma |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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