Polymorphonuclear leukocytes (PMN) accumulating in airways of patients with cystic fibrosis (CF) as a response to chronic endobronchial bacterial lung infection, release lysosomal serine proteinases such as PMN-elastase at concentrations of approximately 0.5 microM to 5 microM into the airway lumen. Immunohistology of CF lung material and fluorescence activated cell sorter analysis of sequential CF bronchoalveolar lavages demonstrated loss of the CD4 and CD8 Ag on CD3+ T lymphocytes in sputum-filled airways. In 10 CF sputum samples 1.0%, 19.1%, and 15.7% of all CD3+ T lymphocytes expressed CD4, CD8, and CD2, respectively. Incubation of CF sputum supernatant fluids with peripheral blood T lymphocytes resulted in total reduction of CD4 and CD8 but not CD2. Addition of alpha 1-proteinase inhibitor abolished surface Ag cleavage completely. Purified PMN-elastase and cathepsin G cleaved CD2, CD4, and CD8 on peripheral blood T lymphocytes at proteinase concentrations of 0.83 to 8.3 microM in a dose-dependent manner. Cleaved CD4 and CD8 were reexpressed on the surface of T lymphocytes after 24 h in the absence of PMN-elastase. Incubation of a CD4+ T cell clone with PMN-elastase lead to a significant reduction of cytotoxicity toward target cells and significantly reduced IL-2 and IL-4 production. The results suggest a temporary functional impairment of T lymphocytes in foci of high inflammation characterized by stimulated PMN, which may lower tissue destruction.