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Development of Spontaneous Airway Changes Consistent with Human Asthma in Mice Lacking T-bet
Susetta Finotto,1Markus F. Neurath,2Jonathan N. Glickman,3Shixin Qin,4Hans A. Lehr,5Francis H. Y. Green,6Kate Ackerman,1Kathleen Haley,1Peter R. Galle,7Susanne J. Szabo,8Jeffrey M. Drazen,18George T. De Sanctis,1Laurie H. Glimcher8*
Human asthma is associated with airway infiltration by T helper 2 (TH2) lymphocytes. We observed reduced expression of
theTH1 transcription factor, T-bet, in T cells from
airways of patientswith asthma compared with that in T cells from
airways of nonasthmaticpatients, suggesting that loss of T-bet might
be associated withasthma. Mice with a targeted deletion of the T-bet
gene and severecombined immunodeficient mice receiving
CD4+ cells from T-bet knockout mice spontaneously
demonstrated multiplephysiological and inflammatory features
characteristic of asthma.Thus, T-bet deficiency, in the absence of
allergen exposure, inducesa murine phenotype reminiscent of both acute
and chronic humanasthma.
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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[DOI: 10.1126/science.295.5553.253a] |Summary »|Full Text »|PDF »
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Susanne J. Szabo, Brandon M. Sullivan, Claudia Stemmann, Abhay R. Satoskar, Barry P. Sleckman, and Laurie H. Glimcher (11 January 2002) Science295 (5553), 338.
[DOI: 10.1126/science.1065543] |Abstract »|Full Text »|PDF »|Supplemental Data »
