| Role of regulatory T cells in long-term immune dysfunction associated with severe sepsis. | |
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MedLine Citation:
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PMID: 20543670 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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OBJECTIVE: To investigate the role of regulatory T cells in the modulation of long-term immune dysfunction during experimental sepsis. It is well established that sepsis predisposes to development of a pronounced immunosuppression. Nevertheless, the mechanisms underlying the immune dysfunction after sepsis are still not well understood. DESIGN: Prospective experimental study. SETTING: University research laboratory. INTERVENTIONS: Wild-type mice underwent cecal ligation and puncture and were treated with antibiotic during 3 days after surgery. On days 1, 7, or 15 after cecal ligation and puncture, the frequency of regulatory T cells, proliferation of CD4 T cells and bacterial counts were evaluated. Fifteen days after cecal ligation and puncture, surviving mice underwent secondary pulmonary infection by intranasal inoculation of nonlethal dose of Legionella pneumophila. Some mice received agonistic glucocorticoid-induced tumor necrosis factor receptor antibody (DTA-1) before induction of secondary infection. MEASUREMENTS AND MAIN RESULTS: Mice surviving cecal ligation and puncture showed a markedly increased frequency of regulatory T cells in thymus and spleen, which was associated with reduced proliferation of CD4 T cells. Fifteen days after cecal ligation and puncture, all sepsis-surviving mice succumbed to nonlethal injection of L. pneumophila. Treatment of mice with DTA-1 antibody reduced frequency of regulatory T cells, restored CD4 T cell proliferation, reduced the levels of bacteria in spleen, and markedly improved survival of L. pneumophila infection. CONCLUSION: These findings suggest that regulatory T cells play an important role in the progression and establishment of immune dysfunction observed in experimental sepsis. |
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Authors:
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Daniele C Nascimento; José C Alves-Filho; Fabiane Sônego; Sandra Y Fukada; Marcelo S Pereira; Claudia Benjamim; Dario S Zamboni; João S Silva; Fernando Q Cunha |
Publication Detail:
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Type: Comparative Study; Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Critical care medicine Volume: 38 ISSN: 1530-0293 ISO Abbreviation: Crit. Care Med. Publication Date: 2010 Aug |
Date Detail:
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Created Date: 2010-07-21 Completed Date: 2010-08-17 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0355501 Medline TA: Crit Care Med Country: United States |
Other Details:
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Languages: eng Pagination: 1718-25 Citation Subset: AIM; IM |
Affiliation:
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Departments of Biochemistry and Immunology, University of São Paulo, Ribeirao Preto, São Paulo, Brazil. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Antigens, CD3 / metabolism Antigens, CD4 / metabolism Aspartate Aminotransferases / metabolism Cell Proliferation Chi-Square Distribution Disease Models, Animal Disease Progression Female Flow Cytometry Hypersensitivity, Delayed / immunology Immune Tolerance* Legionella pneumophila Male Mice Mice, Inbred C57BL Random Allocation Sepsis / immunology*, metabolism, microbiology Statistics, Nonparametric Survival Rate T-Lymphocytes, Regulatory / immunology* |
| Chemical | |
Reg. No./Substance:
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0/Antigens, CD3; 0/Antigens, CD4; EC 2.6.1.1/Aspartate Aminotransferases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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