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The Second Dept of Internal Medicine, Ehime University School of Medicine, Onsen-gun, Ehime, and Dept of Molecular and Internal Medicine, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan
CORRESPONDENCE: A. Yokoyama, Dept of Molecular and Internal Medicine, Graduate School of Biomedical Sciences, Hiroshima University, Kasumi 1-2-3, Minami-ku, Hiroshima 734-8551, Japan. Fax: 81 822557360. E-mail: yokoyan@hiroshima-u.ac.jp
Keywords: Airway responsiveness, asthma, chemokine, eosinophilic inflammation, T-helper cell type 1
Received: February 17, 2004
Accepted December 9, 2004
T-helper cell type 1 (Th1) cells have been postulated to have a significant role in protective immunity against allergic diseases. However, recent studies using polarised Th1 cells showed conflicting effects on both airway responsiveness and eosinophilic inflammation in a mouse asthma model. The current study explored the effects of adoptive transfer of established Th1 clones on a murine model of atopic asthma.
Mice (BALB/c) were sensitised with ovalbumin (OVA) and challenged with aerosolised OVA (5%, 20 min) for 5 days. Just before starting the first challenge, Th1 clones (5x106·body–1) or PBS alone were injected via the tail vein. After assessment of airway responsiveness to methacholine, bronchoalveolar lavage fluid (BALF) was obtained. Histological examination, including morphometric analysis, measurement of cytokines in the BALF and Northern blotting of lung chemokines, was also performed.
Adoptive transfer of Th1 clones showed a significantly increased total number of cells, whereas significantly decreased eosinophils were found in the BALF, when compared with mice with injection of vehicle alone or splenic mononuclear cells. Administration of Th1 clones significantly decreased the infiltration of eosinophils but increased mononuclear cells in the peribronchial area. Goblet cell hyperplasia and peribronchial fibrosis were also suppressed by Th1 clones. The transfer of Th1 cells significantly decreased airway responsiveness. Th1 injection significantly increased interferon gamma in the BALF, but significantly decreased interleukin (IL)-5 and IL-13. Eotaxin mRNA was predominantly expressed in the lungs of asthma model mice, whereas RANTES (regulated on activation, normal T-cell expressed and secreted) predominates in such mice with Th1 transfer.
In conclusion, results suggest that the adoptive transfer of T-helper cell type 1 clones can suppress both lung eosinophilia and airway responsiveness, but increase noneosinophilic inflammation in a mouse model of asthma.
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