Differences in the induction of macrophage cytotoxicity by the specific T lymphocyte factor, specific macrophage arming factor (SMAF), and the lymphokine, macrophage activating factor (MAF).
Specific T cell factors, such as specific macrophage arming factor (SMAF), are involved in the initiation of the immune response. Induction of SMAF-producing T lymphocytes in vivo and of SMAF production by T lymphocytes in vitro is dependent on the presence of intact tumor cells, and is independent of antigen presentation by macrophages. SMAF renders peritoneal macrophages cytotoxic for tumor cells. The armed peritoneal macrophages expressed a specific cytotoxicity. However, antigen-presenting cells can trigger lymphokine-producing T lymphocytes. These T lymphocytes produce lymphokines (e.g. macrophage activating factor (MAF] that activate macrophages. The MAF-activated macrophages express a non-specific tumoricidal activity. In the present study, we investigated the difference in the induction of macrophage cytotoxicity by SMAF and MAF. The following differences were found: 1) SMAF renders peritoneal resident macrophages cytotoxic, whereas MAF could only render peritoneal exudate macrophages cytotoxic. 2) SMAF requires only a 4-h incubation with macrophages, whereas MAF activates macrophages optimally after 12 h. 3) SMAF-armed macrophages recognize only the specific target cell(s), and thus, the cytotoxicity is specific in its expression. MAF activated macrophages were non-specifically cytotoxic. 4) Lipopolysaccharide (LPS) in the culture medium did not enhance the cytotoxicity of SMAF-armed macrophages. In contrast, MAF induced tumoricidal activity was enhanced by adding LPS to the culture medium. 5) After adsorption chromatography with anti-murine interferon-gamma (IFN-gamma), the arming capacity of SMAF supernatant was not reduced, whereas the activating capacity of the MAF supernatant was significantly reduced or abrogated. After immunization of mice with allogeneic tumor cells, SMAF-producing lymphocytes were detected in the draining lymph nodes already 4 days after immunization and up to 12 days. Lymphocytes with the capacity to produce MAF were present in the draining lymph nodes 14-24 days after immunization. Our data indicate that the T cell factors SMAF and MAF can both render macrophages cytotoxic, but act in a different way and during different stages of the cellular immune response against allogeneic tumor cells.
De Groot
J W
JW
Department of Experimental Pathology, Rijksuniversiteit, Utrecht, The Netherlands.
De Weger
R A
RA
Vandebriel
R J
RJ
Den Otter
W
W
D000818:Animals; D000911:Antibodies, Monoclonal; D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D007111:Immunity, Cellular; D008070:Lipopolysaccharides / Q000378:metabolism; D008222:Lymphokines / Q000494:pharmacology*; D008263:Macrophage Migration-Inhibitory Factors / Q000378:metabolism; D016215:Macrophage-Activating Factors; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D008815:Mice, Inbred Strains; D010529:Peritoneal Cavity / Q000166:cytology; D013601:T-Lymphocytes / Q000276:immunology; D013997:Time Factors; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D008070:Lipopolysaccharides; D008222:Lymphokines; D008263:Macrophage Migration-Inhibitory Factors; D016215:Macrophage-Activating Factors