The Journal of Experimental Medicine
Cytokines in immune regulation
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Published 3 June 2002. doi:10.1084/jem.20020028
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© Rockefeller University Press, 0022-1007/2002/6/1471/ $5.00
The Journal of Experimental Medicine, Volume 195, Number 11, June 3, 2002 1471-1478
CD4+ T Cells Regulate Surgical and Postinfectious Adhesion Formation

Doo Ryeon Chung1, Tanuja Chitnis2, Ronald J. Panzo1, Dennis L. Kasper1,4, Mohamed H. Sayegh3 and Arthur O. Tzianabos1

1 Channing Laboratory, Department of Medicine
2 Department of Neurology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115
3 Laboratory of Immunogenetics and Transplantation, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115
4 Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, MA 02115

Address correspondence to Arthur O. Tzianabos, Channing Laboratory, 181 Longwood Avenue, Boston, MA 02115. Phone: 617-525-2610; Fax: 617-731-1541; E-mail: atzianabos{at}channing.harvard.edu

The development of adhesions in the peritoneal and pelvic cavities, which commonly form after surgery or infection, cause significant morbidity and mortality. However, the pathogenesis of adhesion formation is still poorly understood. Because T cells are important in orchestrating fibrinogenic tissue disorders, we hypothesized that they play a critical role in the pathogenesis of peritoneal adhesion formation. Using a cecal abrasion surgical model in rodents, T cell depletion and adoptive transfer experiments demonstrated that this host response is dependent on CD4+ {alpha}ß T cells. These cells were also critical to adhesion formation associated with experimental intraabdominal sepsis. T cell transfer studies with mice deficient in signal transducer and activator of transcription (Stat)4 and Stat6 revealed that adhesion formation was dependent on a T helper 1 response. Activated T cells homed to the peritoneal cavity 6 hours after cecal abrasion surgery and predominated at this site during adhesiogenesis. Increased levels of the T cell–derived proinflammatory cytokine interleukin (IL)-17 and of neutrophil chemoattractant CXC chemokines macrophage inflammatory protein-2/CXCL8 and cytokine-induced neutrophil chemoattractant/CXCL1 were associated with adhesion formation. The production of these chemokines was dependent on T cells. Furthermore, the administration of neutralizing antibodies specific for IL-17 or the receptor that binds these CXC chemokines, CXC chemokine receptor 2, significantly reduced the degree of adhesion formation. These results demonstrate for the first time that the immunopathogenesis of adhesion formation is under the control of T cells and that T cell–derived cytokines and chemokines play important roles in the development of this deleterious host response.

Key Words: T cells • adhesions • interleukin-17 • chemokines • peritonitis


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