CD4+ T cells mediate abscess formation in intra-abdominal sepsis by an IL-17-dependent mechanism.

Abstract

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.

• Authors: Doo Ryeon Chung, Dennis L Kasper, Ronald J Panzo, Tanuja Chitnis, Michael J Grusby, Mohamed H Sayegh, Arthur O Tzianabos, Tanuja Chtinis
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 170 Issue 4 Pg. 1958-63 (Feb 15 2003) ISSN: 0022-1767 [Print] United States
• PMID: 12574364 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antigens, CD
• B7-1 Antigen
• B7-2 Antigen
• CD28 Antigens
• Cd86 protein, mouse
• DNA-Binding Proteins
• Immune Sera
• Interleukin-17
• Membrane Glycoproteins
• STAT4 Transcription Factor
• STAT6 Transcription Factor
• Stat4 protein, mouse
• Stat6 protein, mouse
• Trans-Activators

Topics

• Abdominal Abscess (genetics, immunology, pathology, prevention & control)
• Animals
• Antigens, CD (physiology)
• B7-1 Antigen (physiology)
• B7-2 Antigen
• Bacteroides Infections (genetics, immunology, pathology, prevention & control)
• Bacteroides fragilis (immunology)
• CD28 Antigens (genetics, physiology)
• CD4-Positive T-Lymphocytes (immunology, metabolism)
• Cell Movement (genetics, immunology)
• DNA-Binding Proteins (deficiency, genetics, physiology)
• Immune Sera (administration & dosage)
• Immunity, Cellular (genetics)
• Immunophenotyping
• Interleukin-17 (antagonists & inhibitors, biosynthesis, immunology, physiology)
• Kinetics
• Membrane Glycoproteins (physiology)
• Mice
• Mice, Inbred BALB C
• Mice, Inbred C57BL
• Mice, Knockout
• Peritoneal Cavity (microbiology, pathology)
• STAT4 Transcription Factor
• STAT6 Transcription Factor
• Sepsis (genetics, immunology, pathology)
• Signal Transduction (genetics, immunology)
• Trans-Activators (deficiency, genetics, physiology)