Immune complexes from immunized mice and infected cystic fibrosis patients mediate murine and human T cell killing of hybridomas producing protective, opsonic antibody to Pseudomonas aeruginosa

• Published in: The Journal of clinical investigation Vol. 91; no. 3; pp. 1079 - 1087
• Main Authors: PIER, G. B, TAKEDA, S, GROUT, M, MARKHAM, R. B
• Format: Journal Article
• Language: English
• Published: Ann Arbor, MI American Society for Clinical Investigation 01.03.1993
• Subjects: Animals; Antibodies, Bacterial - immunology; Antigen-Antibody Complex - blood; Antigen-Antibody Complex - immunology; Antigens, CD - analysis; B-Lymphocytes - immunology; Bacterial diseases; Bacterial diseases of the respiratory system; Biological and medical sciences; Cystic Fibrosis - blood; Cystic Fibrosis - complications; Cystic Fibrosis - immunology; Cytotoxicity, Immunologic; Human bacterial diseases; Humans; Hybridomas - immunology; Infectious diseases; Medical sciences; Mice; Pseudomonas aeruginosa; Pseudomonas aeruginosa - immunology; Pseudomonas Infections - blood; Pseudomonas Infections - complications; Pseudomonas Infections - immunology; Receptors, Antigen, T-Cell - analysis; T-Lymphocytes - immunology; T-Lymphocytes, Cytotoxic - immunology; Infection; Pseudomonadales; Human; Mucoviscidosis; Pathophysiology; Respiratory disease; Lung; Bacteriosis; Bacteria; Pseudomonadaceae; Pseudomonas aeruginosa
• ISSN: 0021-9738; 1558-8238
• DOI: 10.1172/JCI116265

We examined the basis for the absence in cystic fibrosis (CF) patients of opsonic antibodies to the mucoid exopolysaccharide (MEP) antigen surrounding Pseudomonas aeruginosa that infect these patients. Opsonic antibodies to MEP are found in sera of the minority of CF patients that remain noncolonized into the second to fourth decades of life and protect rodents from chronic P. aeruginosa endobronchial infections. High titers of nonopsonic antibodies to MEP are found in P. aeruginosa-infected CF patients. Immunization of mice with doses of MEP that provoke only nonopsonic antibodies elicited CD3+, CD8+, T cell receptor alpha beta receptor+, major histocompatibility complex-unrestricted cytotoxic lymphocytes specific for hybridoma cells producing opsonic but not nonopsonic antibodies. Cytotoxicity was dependent on immune complexes on the surface of the T cells. Normal murine T cells could be activated by concanavalin A and sensitized with immune complexes for cytotoxic killing of hybridoma targets. CF patients infected with P. aeruginosa had serum immune complexes that sensitized concanavalin A-activated human T cells to kill murine hybridoma cells producing opsonic but not nonopsonic antibody. These results could explain the absence in infected CF patients of MEP-specific opsonins, an occurrence that accompanies the persistence of this infectious state.