Generation and characterization of cytotoxic activity against tumor cell lines in human peripheral blood mononuclear cells stimulated "in vitro" by a glucomannan-protein preparation of Candida albicans.
Human peripheral blood mononuclear cells (PBMC) proliferated and generated non-specific cell-mediated cytotoxicity (CMC) after stimulation with a cell-wall glucomannan-protein (GMP) fraction of Candida albicans or chemically-inactivated intact microrganism. No effects were observed using other fungal cell wall components such as glucan or alkali-acid treated glucomannan. The highest CMC level was detected after 7-10 days of PBMC incubation in the presence of 50 micrograms/ml of whole Candida cells and the cytotoxic immunoeffectors elicited by these antigenic stimulations equally affected NK-susceptible (K562) and NK-resistant (Raji, Daudi and Jurkat) tumor cell lines. Both Interleukin-2 (IL-2) and gamma interferon (IFN-gamma) were produced by GMP-stimulated PBMC, the IL-2 peak production constantly preceding that of IFN production. GMP-induced generation of natural CMC was potentiated by the addition of IFN-gamma and a monospecific anti IFN-gamma serum totally abrogated both IFN activity and CMC generation. The cytolytic effectors were shown to be OKT3-, OKT8- and HLA-DR-. They did not possess typical NK markers (e.g. Leu-7 and AB8.28) but were partially recognized by A10, a IgG2a monoclonal antibody reacting to PBMC-NK lymphocytes and activated T cells. These results suggest that the antitumor cytolytic effectors generated in PBMC cultures exposed to Candida material belong either to a discrete subset of natural effectors lacking classical NK markers or to other lymphokine-activated cells. This study also suggests that the human indigenous microrganisms C.albicans may play a role in raising nonspecific antitumor effects in normal host.
D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D002176:Candida albicans / Q000648:ultrastructure*; D002460:Cell Line; D002473:Cell Wall / Q000032:analysis; D003603:Cytotoxins / Q000494:pharmacology / Q000633:toxicity*; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008351:Mannans; D014407:Tumor Cells, Cultured / Q000187:drug effects* / Q000276:immunology
D000276:Adjuvants, Immunologic; D003603:Cytotoxins; D007376:Interleukin-2; D008351:Mannans; C022901:(1-6)-alpha-glucomannan; D007371:Interferon-gamma