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Original Article


Intranasal Delivery of T-bet Modulates the Profile of Helper T Cell Immune Responses in Experimental Asthma


SY Wang,1,2 M Yang,2 XP Xu,2 GF Qiu,2 J Ma,2 SJ Wang,2 XX Huang,2 HX Xu2

1 Department of Pediatrics, Affi liated Hospital of Jiangsu University, Zhenjiang, Jiangsu, China
2 Institute of Clinical Laboratory Science, Jiangsu University, School of Medical Technology, Zhenjiang, Jiangsu, China

J Investig Allergol Clin Immunol 2008; Vol. 18(5): 357-365



Background: Allergic asthma is caused by aberrant helper T (TH) type 2 immune responses in susceptible individuals, characterized by airway hyperresponsiveness, chronic airway inflammation, and mucus hypersecretion. Its prevalence continues to increase, but optimal treatment remains a challenge. The transcription factor T-bet is a master regulator of TH1 lineage commitment and strongly promotes interferon γ
expression during TH1 cell differentiation.

Objective: The aim of this study was to explore the role of intranasal delivery of T-bet on the differentiation of TH cell subsets and airway inflammation in the ovalbumin (OVA)-induced mouse model of allergic airway inflammation.

Methods: BALB/c mice were sensitized by intraperitoneal injection of OVA and challenged with nebulized OVA. Four days before the inhalation challenge, the sensitized mice were subjected to intranasal delivery of a recombinant adeno-associated virus vector carrying
murine T-bet gene (AAV-T-bet). Expression of the transcription factors T-bet, GATA3, and Foxp3 was then assayed in the lungs, and airway histology was analyzed along with other infl ammatory parameters, such as eosinophils and cytokines in bronchoalveolar lavage (BAL) fluid, and total and OVA-specific immunoglobulin (Ig) E in serum.

Results: Intranasal administration of AAV-T-bet efficiently balanced the TH1/TH2 transcription factor and cytokine profi le and significantly decreased the number of eosinophils in BAL fluid. It also resulted in a reduction of peribronchial inflammation scores and serum IgE levels in OVA-sensitized and challenged mice during the effector phase.

Conclusions: Our data show that intranasal delivery of T-bet can promote a TH1 immune response, restore a balanced Th immune response,
and inhibit airway inflammation during the challenge phase in a mouse model of allergic airway inflammation.

Key words: Allergy. Transcription factor. Modulation. Immune response. TH1/TH2.