T-CELL LUNG GRANULOMAS INDUCED BY SEPHAROSE-COUPLED MYCOBACTERIUM-TUBERCULOSIS PROTEIN ANTIGENS - IMMUNOSUPPRESSIVE PHENOMENA REVERSED WITHCYCLOPHOSPHAMIDE AND INDOMETHACIN

We induced lung granulomas in BALB/c mice by intratracheal instillatio n of Sepharose beads coated with a Mycobacterium tuberculosis protein extract. Granulomas composed of macrophages and lymphocytes were induc ed. The granulomatous reaction reached its peak 3-7 days after challen ge and lasted for approximately 1 month. Immunolabelling of tissue sec tions and bronchial washings revealed that granulomas were predominant ly composed of T lymphocytes with the cytotoxic-suppressor phenotype ( CD8(+)). Granulomas were associated with a significant decrease in ant i-mycobacterial immunity manifested by a drop in delayed-type hypersen sitivity reactions and antibody titres. The immunosuppressive phenomen a were abolished with cyclophosphamide or indomethacin. Control granul omas induced with methylated bovine serum albumin (BSA) were smaller a nd composed by similar numbers of CD4(+) and CD8(+) cells. BSA granulo mas did not alter antibody titres but they decreased delayed-type hype rsensitivity to BSA which was restored to normal with indomethacin but not with cyclophosphamide. Our findings show that mycobacterial prote ins anchored to Sepharose beads are granulomatogenic and that they pre ferentially recruit CD8(+) cells which, together with locally produced prostaglandins, down-modulate cell-mediated and humoral immunity to m ycobacterial antigens.