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Eur Respir J 2003; 21:11-18
Copyright ©ERS Journals Ltd 2003


T-helper 1 cells induce alveolitis but do not lead to pulmonary fibrosis in mice

K. Irifune, A. Yokoyama, N. Kohno, K. Sakai and K. Hiwada

The Second Dept of Internal Medicine, Ehime University School of Medicine, Onsen-gun, Ehime, Japan

CORRESPONDENCE: A. Yokoyama, Second Dept of Internal Medicine, Shigenobu, Onsen-gun, Ehime, 791-0295, Japan. Fax: 81 899605306. E-mail: yokoyan@m.ehime-u.ac.jp

Keywords: cytokine, hypersensitivity pneumonitis, sarcoidosis, T-helper 1/T-helper 2

Received: October 31, 2001
Accepted May 22, 2002

T-helper (Th)1 cells have a pivotal role in the pathogenesis of hypersensitivity pneumonitis. Continued low-level exposure to the antigens may induce chronic hypersensitivity pneumonitis with lung fibrosis. Although such exposure may activate Th1 cells in the lung, it is not known whether activation of Th1 cells per se can lead to pulmonary fibrosis. To determine this, the lung pathology induced by Th1 clones was investigated.

Mice (BALB/c) were injected intraperitoneally with Th1 clones 1–4 times. Each injection was performed 4 days apart and was followed by repeated exposure to aerosolised ovalbumin (OVA) once a day for 5 days.

The number of macrophages and lymphocytes in bronchoalveolar lavage fluids (BALF) increased as the number of Th1 transfers increased. The number of neutrophils also increased but peaked in the second transfer and then decreased following further transfers. Increased cell infiltration, thickness of alveolar walls and number of type II cells in the lung occurred. However, histological findings showed no evidence of fibrosis and hydroxyproline levels did not increase. Findings of histology and BALF were ameliorated 2 weeks after the discontinuation of OVA exposure, indicating the reversibility of the Th1-induced pathology.

In conclusion, adoptive transfer of T-helper 1 cells results in reversible alveolitis but does not lead to pulmonary fibrosis.




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