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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
4
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pubmed:dateCreated |
2003-2-7
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pubmed:abstractText |
Abscess formation associated with intra-abdominal sepsis causes severe morbidity and can be fatal. Previous studies have implicated T cells in the pathogenesis of abscess formation, and we have recently shown that CD4(+) T cells activated in vitro by zwitterionic capsular polysaccharides from abscess-inducing bacteria such as Staphylococcus aureus and Bacteroides fragilis initiate this host response when transferred to naive rats. In this study, we show that mice deficient in alphabetaTCR-bearing T cells or CD4(+) T cells fail to develop abscesses following challenge with B. fragilis or abscess-inducing zwitterionic polysaccharides, compared with CD8(-/-) or wild-type animals. Transfer of CD4(+) T cells from wild-type mice to alphabetaTCR(-/-) animals reconstituted this ability. The induction of abscesses required T cell costimulation via the CD28-B7 pathway, and T cell transfer experiments with STAT4(-/-) and STAT6(-/-) mice demonstrated that this host response is dependent on STAT4 signaling. Significantly higher levels of IL-17, a proinflammatory cytokine produced almost exclusively by activated CD4(+) T cells, were associated with abscess formation in Th2-impaired (STAT6(-/-)) mice, while STAT4(-/-) mice had significantly lower levels of this cytokine than control animals. The formation of abscesses was preceded by an increase in the number of activated CD4(+) T cells in the peritoneal cavity 24 h following bacterial challenge. Confocal laser-scanning microscopy analysis revealed that CD4(+) T cells comprise the abscess wall in these animals and produce IL-17 at this site. Administration of a neutralizing Ab specific for IL-17 prevented abscess formation following bacterial challenge in mice. These data delineate the specific T cell response necessary for the development of intra-abdominal abscesses and underscore the role of IL-17 in this disease process.
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pubmed:grant |
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pubmed:commentsCorrections |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
AIM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD28,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD80,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD86,
http://linkedlifedata.com/resource/pubmed/chemical/Cd86 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Immune Sera,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-17,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Glycoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/STAT4 Transcription Factor,
http://linkedlifedata.com/resource/pubmed/chemical/STAT6 Transcription Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Stat4 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Stat6 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Trans-Activators
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pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
0022-1767
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
15
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pubmed:volume |
170
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1958-63
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:12574364-Abdominal Abscess,
pubmed-meshheading:12574364-Animals,
pubmed-meshheading:12574364-Antigens, CD,
pubmed-meshheading:12574364-Antigens, CD28,
pubmed-meshheading:12574364-Antigens, CD80,
pubmed-meshheading:12574364-Antigens, CD86,
pubmed-meshheading:12574364-Bacteroides Infections,
pubmed-meshheading:12574364-Bacteroides fragilis,
pubmed-meshheading:12574364-CD4-Positive T-Lymphocytes,
pubmed-meshheading:12574364-Cell Movement,
pubmed-meshheading:12574364-DNA-Binding Proteins,
pubmed-meshheading:12574364-Immune Sera,
pubmed-meshheading:12574364-Immunity, Cellular,
pubmed-meshheading:12574364-Immunophenotyping,
pubmed-meshheading:12574364-Interleukin-17,
pubmed-meshheading:12574364-Kinetics,
pubmed-meshheading:12574364-Membrane Glycoproteins,
pubmed-meshheading:12574364-Mice,
pubmed-meshheading:12574364-Mice, Inbred BALB C,
pubmed-meshheading:12574364-Mice, Inbred C57BL,
pubmed-meshheading:12574364-Mice, Knockout,
pubmed-meshheading:12574364-Peritoneal Cavity,
pubmed-meshheading:12574364-STAT4 Transcription Factor,
pubmed-meshheading:12574364-STAT6 Transcription Factor,
pubmed-meshheading:12574364-Sepsis,
pubmed-meshheading:12574364-Signal Transduction,
pubmed-meshheading:12574364-Trans-Activators
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pubmed:year |
2003
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pubmed:articleTitle |
CD4+ T cells mediate abscess formation in intra-abdominal sepsis by an IL-17-dependent mechanism.
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pubmed:affiliation |
Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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