Th2 cells as effectors in postirradiation pulmonary damage preceding fibrosis in the rat

Purpose : Radiation-induced pneumonitis and subsequent pulmonary fibrosis are important dose-limiting complications of radiotherapy. Their pathogenesis is known onlyin part. T-lymphocytes comprise a significant part of the infiltrating cells but little is known about their role. The aim of this stud...

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Bibliographic Details
Published in:International journal of radiation biology 1999, Vol.75 (5), p.629-638
Main Author: WESTERMANN, R. SCHOBL, E. P. RIEBER, K.-H. FRANK, W.
Format: Article
Language:English
Subjects:
AIDS/HIV
Animals
Biological and medical sciences
Interferon-gamma - genetics
Interleukin-4 - genetics
Lung - radiation effects
Male
Medical sciences
Pneumology
Pneumonia - etiology
Pulmonary Fibrosis - etiology
Rats
Rats, Inbred F344
Respiratory system : syndromes and miscellaneous diseases
RNA, Messenger - analysis
Space life sciences
Th2 Cells - physiology
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Summary:Purpose : Radiation-induced pneumonitis and subsequent pulmonary fibrosis are important dose-limiting complications of radiotherapy. Their pathogenesis is known onlyin part. T-lymphocytes comprise a significant part of the infiltrating cells but little is known about their role. The aim of this study was to define the function of T-lymphocytes during development of postirradiation pneumonitis and pulmonary fibrosis. Materials and methods : Rats received a unilateral lung irradiation of 20Gy. Kinetics of T-lymphocytes isolated from irradiated and non-irradiated lungs were analysed. Subsequent CD4 depletion experiments were performed to affirm the importance of CD4 T-cells in the development of lung fibrosis. Finally, the T helpercell subtype of the T-lymphocytes was analysed by determining the cytokine mRNA by RT-PCR. Results : A selective increase of CD4 T-cells was observed peaking 4 weeks after irradiation in the irradiated lungs. When rats were depleted of these cells, the postirradiation thickening of parenchyma was significantly reduced as determined by morphometric analysis of lung tissue sections. In addition, it was found that IL-4 mRNA was selectively increased in the CD4 T-cells isolated from irradiated lungs, which indicates a lymphocyte reactivity dominated by Th2 cells. Conclusion : The results suggest a critical role for Th2 CD4 T-lymphocytes in the pathogenesis of radiation-induced pneumonitis preceding lung fibrosis.
ISSN:0955-3002
1362-3095
DOI:10.1080/095530099140276