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A more recent version of this article appeared on January 1, 2007

Published online before print October 13, 2006
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© by The Society for Leukocyte Biology
Journal of Leukocyte Biology, doi:10.1189/jlb.1105696


Received for publication November 29, 2005.
Revised July 26, 2006.
Accepted for publication August 19, 2007.


Article

Aggravation of intestinal inflammation by depletion/deficiency of {gamma}{delta} T cells in different types of IBD animal models

Anja A. Kühl *, Nina N. Pawlowski *, Katja Grollich *, Christoph Loddenkemper , Martin Zeitz *, and Jörg C. Hoffmann *@

*Medizinische Klinik I, Universitätsmedizin Berlin, Campus Benjamin Franklin, Berlin, Germany; and {dagger}Institute of Pathology, Charité, University Medicine Berlin, Campus Benjamin Franklin, Berlin, Germany

@ To whom correspondence should be addressed. E-mail: joerg.hoffmann{at}charite.de.


   Abstract

The role of {gamma}{delta} T cells in inflammatory bowel disease (IBD) is still controversial. Although {gamma}{delta} T cells induce IBD in immunodeficient animals, others suggest a protective role of {gamma}{delta} T cells. Therefore, this study was conducted in order to elucidate the effect of {gamma}{delta} T cell depletion/deficiency on different IBD animal models. Mice depleted of or deficient in {gamma}{delta} T cells were exposed to dextran sodium sulfate (DSS) in order to induce colitis. In addition, {gamma}{delta} T cells were depleted in mice with terminal ileitis (TNF{Delta}ARE) or colitis due to interleukin 2 deficiency (IL-2 ko). Finally, DSS-induced colitis was studied in mice deficient in interferon gamma (IFN-{gamma} ko) upon {gamma}{delta} T cell depletion. Depletion of {gamma}{delta} T cells aggravated DSS-induced colitis and terminal ileitis of TNF{Delta}ARE mice. Exacerbated DSS-induced colitis was also found in {gamma}{delta} T cell-deficient mice. IL-2 ko mice showed increased mortality upon early (starting at 4 wk of age) but not late depletion (starting at 8 wk of age). Early {gamma}{delta} T cell depletion or deficiency resulted in increased IFN-{gamma} production by both lamina propria lymphocytes and splenocytes in every model investigated herein. In IFN-{gamma} ko mice, {gamma}{delta} T cell depletion did not affect the development and course of DSS-induced colitis. The protective effect of {gamma}{delta} T cells in IBD was confirmed in various IBD animal models. Particularly, during the early phase of intestinal inflammation, {gamma}{delta} T cells appear to be important. The mechanism seems to involve the control of IFN-{gamma} production and epithelial regeneration.

Key Words: colitis • epithelial regeneration • interferon {gamma} • terminal ileitis







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