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CD4+ T helper cells engineered to produce latent TGF-β1 reverse allergen-induced airway hyperreactivity and inflammation
Gesine Hansen, … , Rosemarie H. DeKruyff, Dale T. Umetsu
Gesine Hansen, … , Rosemarie H. DeKruyff, Dale T. Umetsu
Published January 1, 2000
Citation Information: J Clin Invest. 2000;105(1):61-70. https://doi.org/10.1172/JCI7589.
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CD4+ T helper cells engineered to produce latent TGF-β1 reverse allergen-induced airway hyperreactivity and inflammation

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Abstract

T helper 2 (Th2) cells play a critical role in the pathogenesis of asthma, but the precise immunological mechanisms that inhibit Th2 cell function in vivo are not well understood. Using gene therapy, we demonstrated that ovalbumin-specific (OVA-specific) Th cells engineered to express latent TGF-β abolished airway hyperreactivity and airway inflammation induced by OVA-specific Th2 effector cells in SCID and BALB/c mice. These effects correlated with increased concentrations of active TGF-β in the bronchoalveolar lavage (BAL) fluid, demonstrating that latent TGF-β was activated in the inflammatory environment. In contrast, OVA-specific Th1 cells failed to inhibit airway hyperreactivity and inflammation in this system. The inhibitory effect of TGF-β–secreting Th cells was antigen-specific and was reversed by neutralization of TGF-β. Our results demonstrate that T cells secreting TGF-β in the respiratory mucosa can indeed regulate Th2-induced airway hyperreactivity and inflammation and suggest that TGF-β–producing T cells play an important regulatory role in asthma.

Authors

Gesine Hansen, Jennifer J. McIntire, V. Peter Yeung, Gerald Berry, G. Jeanette Thorbecke, Lizhen Chen, Rosemarie H. DeKruyff, Dale T. Umetsu

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TGF-β–producing cells inhibit airway hyperreactivity in OVA-immunized BA...
TGF-β–producing cells inhibit airway hyperreactivity in OVA-immunized BALB/c mice. BALB/c mice were immunized with OVA (50 μg) in alum intraperitoneally on day 0 and intranasally (50 μg OVA in 50 μL PBS) on days 7, 8, and 9. Another group of mice was immunized with KLH rather than OVA (KLH, 25 μg intraperitoneally in alum; and KLH, 25 μg in PBS, 50 μL, intranasally). Mice from both groups received OVA-specific TGF-β–producing cells (2.5 × 106 cells/mouse) intravenously on day 7. Some of the OVA-immunized mice received OVA-specific Th1 cells (2.5 × 106 cells/mouse) intravenously on day 7. Airway hyperreactivity in response to inhaled methacholine was measured in a whole-body plethysmograph on day 10 (n = 5 for each data point). Results are demonstrated as mean percent above baseline (± SEM).

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ISSN: 0021-9738 (print), 1558-8238 (online)

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Referenced in 4 patents
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