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

Radiation-induced pneumonitis and subsequent pulmonary fibrosis are important dose-limiting complications of radiotherapy. Their pathogenesis is known only in 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.

Rats received a unilateral lung irradiation of 20 Gy. 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 helper-cell subtype of the T-lymphocytes was analysed by determining the cytokine mRNA by RT-PCR.

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.

The results suggest a critical role for Th2 CD4+ T-lymphocytes in the pathogenesis of radiation-induced pneumonitis preceding lung fibrosis.