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Infection and Immunity, August 2006, p. 4673-4684, Vol. 74, No. 8
0019-9567/06/$08.00+0     doi:10.1128/IAI.01887-05
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Role of Transcription Factor T-bet Expression by CD4+ Cells in Gastritis Due to Helicobacter pylori in Mice

Kathryn A. Eaton,* Lucy H. Benson, Jennifer Haeger, and Brian M. Gray

University of Michigan, Ann Arbor, Michigan 48109

Received 17 November 2005/ Returned for modification 4 April 2006/ Accepted 18 May 2006

Gastritis due to Helicobacter pylori is induced by a Th1-mediated response that is CD4 cell and gamma interferon (IFN-{gamma}) dependent. T-bet is a transcription factor that directs differentiation of and IFN-{gamma} secretion by CD4+ Th1 T cells. The goal of this study was to use two mouse models to elucidate the role of T-bet in gastritis due to H. pylori. C57BL/6J mice, congenic T-bet knockout (KO) mutants, or congenic SCID (severe, combined immunodeficient) mutants were given live H. pylori by oral inoculation. SCID mice were given CD4+ splenocytes from C57BL/6J or T-bet KO mice by intraperitoneal injection. Twelve or 24 weeks after bacterial inoculation, C57BL/6J mice developed moderate gastritis but T-bet KO mice and SCID mice did not. In contrast, SCID recipients of either C57BL/6J T cells or T-bet KO T cells developed gastritis 4 or 8 weeks after adoptive transfer. In recipients of C57BL/6J CD4+ cells but not recipients of T-bet KO cells, gastritis was associated with a delayed-type hypersensitivity response to H. pylori antigen and elevated gastric and serum IFN-{gamma}, interleukin 6, and tumor necrosis factor alpha. In spite of the absence of IFN-{gamma} expression, indicating failure of Th1 differentiation, CD4+ T cells from T-bet KO mice induce gastritis in H. pylori-infected recipient SCID mice. This indicates that Th1-independent mechanisms can cause gastric inflammation and disease due to H. pylori.

* Corresponding author. Mailing address: Unit for Laboratory Animal Medicine, 108 Animal Research Facility, 1150 W. Medical Center Drive, Ann Arbor, MI 48109-0614. Phone: (734) 936-3883. Fax: (734) 936-3235. E-mail: kateaton{at}umich.edu.

Editor: W. A. Petri, Jr.

Infection and Immunity, August 2006, p. 4673-4684, Vol. 74, No. 8
0019-9567/06/$08.00+0     doi:10.1128/IAI.01887-05
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



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