The macrophage aggregation assay for cell-mediated immunity in man. Studies of patients with Hodgkin's disease and sarcoidosis.

Abstract

Abstract A new in vitro method for testing cell-mediated immunity in man was compared with delayed hypersensitivity skin tests and tritiated thymidine incorporation by peripheral blood lymphocytes in response to antigen. Aggregation of guinea pig peritoneal exudate cells was observed after incubation with supernatant fluids from cultures of sensitive human peripheral blood lymphocytes with specific antigens. Candida albicans , PPD, histoplasmin, and streptolysin O were utilized in the in vitro studies. Candida, PPD, histoplasmin, trichophyton, mumps, and streptokinase-streptodornase were used for delayed hypersensitivity skin tests. In normal adults tested with candida, PPD, and histoplasmin, the presence of macrophage aggregation factor (MAF) correlated with tritiated thymidine incorporation in 82 per cent and with skin test results in 84 per cent of the tests. Streptolysin O stimulated MAF synthesis in 19 of 20 normal adults and all showed an increase in DNA synthesis. In contrast, the in vitro and in vivo responses were diminished in 14 patients with Hodgkin's disease and 28 patients with sarcoidosis. Twenty-one per cent of the patients with Hodgkin's disease and 50 per cent of the patients with sarcoidosis reacted to one or more of the skin-test antigens. MAF activity was observed in 28 per cent of the patients with Hodgkin's disease and 32 per cent of those patients with sarcoidosis. Lymphocytes from 64 per cent of the Hodgkin's patients and 61 per cent of the sarcoid patients synthesized DNA in response to antigen. While antigen-stimulated DNA synthesis by lymphocytes appears to reflect a cellular recognition phenomenon which may not be limited to cell-mediated reactions, the macrophage aggregation assay has been shown to correlate with delayed hypersensitivity in the guinea pig. Its adaptation for the study of cell-mediated immunologic functions in man provides a new approach to immunodeficiency and autoimmune diseases.