STRUCTURAL AND FUNCTIONAL CONSEQUENCES OF ALVEOLAR CELL RECOGNITION BY CD8(-LYMPHOCYTES IN EXPERIMENTAL LUNG-DISEASE() T)

CD8(+) T cells infiltrate the lung in many clinical conditions, partic ularly in interstitial lung disease. The role(s) that CD8(+) T cells m ight be playing in the pathogenesis of inflammatory lung disease is un clear at present, as is the direct contribution of CD8(+) T cell effec tor activities to lung injury. This report describes a transgenic mode l used to evaluate the impact, on respiratory structure and function, of CD8(+) T lymphocyte recognition of a target antigen expressed endog enously in alveolar epithelial cells. We found that adoptive transfer of cloned CD8(+) cytotoxic T lymphocytes (CTLs) specific for an alveol ar mo-antigen (influenza hemagglutinin) leads to progressive lethal in jury in transgenic mice, which dramatically affects lung structure and function. Transgenic recipients of CD8(+) CTLs exhibited tachypnea an d progressive weight loss, becoming moribund over a period of several days. Concomitantly, the animals developed a progressive interstitial pneumonitis characterized initially by lymphocytic infiltration of alv eolar walls and spaces, followed by an exuberant mononuclear cell infi ltration that correlated with restrictive pulmonary mechanics and a pr ogressive diffusion impairment, These results indicate that antigen-sp ecific CD8(+) T cell recognition of an alveolar epithelial ''autoantig en'' is, in and of itself, sufficient to trigger an inflammatory casca de that results in the histological and physiological manifestations o f interstitial pneumonia.