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Science 11 January 2002:
Vol. 295. no. 5553, pp. 336 - 338
DOI: 10.1126/science.1065544
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Reports

Development of Spontaneous Airway Changes Consistent with Human Asthma in Mice Lacking T-bet

Susetta Finotto,1 Markus F. Neurath,2 Jonathan N. Glickman,3 Shixin Qin,4 Hans A. Lehr,5 Francis H. Y. Green,6 Kate Ackerman,1 Kathleen Haley,1 Peter R. Galle,7 Susanne J. Szabo,8 Jeffrey M. Drazen,18 George T. De Sanctis,1 Laurie H. Glimcher8*

Human asthma is associated with airway infiltration by T helper 2 (TH2) lymphocytes. We observed reduced expression of the TH1 transcription factor, T-bet, in T cells from airways of patients with asthma compared with that in T cells from airways of nonasthmatic patients, suggesting that loss of T-bet might be associated with asthma. Mice with a targeted deletion of the T-bet gene and severe combined immunodeficient mice receiving CD4+ cells from T-bet knockout mice spontaneously demonstrated multiple physiological and inflammatory features characteristic of asthma. Thus, T-bet deficiency, in the absence of allergen exposure, induces a murine phenotype reminiscent of both acute and chronic human asthma.

1 Critical Care and Pulmonary Division,
2 Division of Gastroenterology,
3 Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
4 Millenium Pharmaceuticals, Cambridge, MA 02138, USA.
5 Department of Pathology, University of Mainz, Mainz 55131, Germany.
6 Department of Pathology and Laboratory Medicine University of Calgary, Alberta, Canada T2N 4N1.
7 Medical Clinic I, University of Mainz, Mainz 55131, Germany.
8 Harvard School of Public Health and Harvard Medical School, Harvard Medical School, Boston, MA 02115, USA.
*   To whom correspondence should be addressed. E-mail lglimche{at}hsph.harvard.edu

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Central Molecule in Asthma Identified: T-bet.
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Distinct Effects of T-bet in TH1 Lineage Commitment and IFN-gamma Production in CD4 and CD8 T Cells.
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The Transcription Factor T-bet Regulates Mucosal T Cell Activation in Experimental Colitis and Crohn's Disease.
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