Impairment of bleomycin-induced lung fibrosis in CD28-deficient mice

Lung fibrosis is an important pulmonary disease with a high mortality rate, but its pathophysiological mechanism has not been fully clarified. Various types of cells have been implicated in the development of lung fibrosis, i ncluding T cells. However, the contribution of functional molecules express ed on T cells to the development of lung fibrosis remains largely unknown. In this study, we determined whether costimulation via CD28 on T cells was crucial for the development of lung fibrosis by intratracheally administeri ng bleomycin into CD28-deficient mice. Compared with wild-type mice, the CD 28-deficient mice showed markedly impaired lung fibrosis after injection wi th low doses of bleomycin, as judged by histological changes and hydroxypro line content in the lungs. In addition, bleomycin-induced T cell infiltrati on into the airways and production of several cytokines and chemokines incl uding IL-5 were also impaired in the CD28-deficient mice. Furthermore, adop tive transfer of CD28-positive T cells from wild-type mice recovered the im paired bleomycin-induced lung fibrosis in CD28-deficient mice. These findin gs suggest that the CD28-mediated T cell costimulation plays a critical rol e in the development of lung fibrosis, possibly by regulating the productio n of cytokines and chemokines in the lung. Thus, manipulation of the CD28-m ediated costimulation could be a potential therapeutic strategy for the pre vention of lung fibrosis. The Journal of Immunology, 2001.