Hydrocortisone suppresses the generation of nonspecific "anomalous" killers but not specific cytolytic T lymphocytes in human mixed lymphocyte-tumor cultures.
Interpretation of results with the use of effector populations generated in human mixed lymphocyte tumor cultures (MLTC) has in many cases been clouded by the presence of two distinct cytolytic effectors: specific cytolytic T lymphocytes (CTL) and nonspecific anomalous killers (AK). The addition of 5 to 50 X 10(-6) M hydrocortisone sodium succinate (HC) to "three-cell" allogeneic human MLTC containing responder lymphocytes, irradiated allogeneic glioma cells, and irradiated third-party stimulator lymphocytes consistently reduced the generation of AK by greater than 90% while having little or no effect on the generation of CTL specific for antigens present on the glioma cells. HC was similarly effective in blocking the generation of AK when added to cultures of responder cells incubated with lymphokine-containing supernatants from mixed lymphocyte cultures. Kinetic experiments indicated that HC both decreased the initial rate of appearance of AK activity and subsequently caused the AK response to decline more rapidly. HC had only a small inhibitory effect on the lytic action of AK generated in its absence. The ability of HC to suppress strongly the generation of nonspecific but not specific cytolytic effectors suggests that nonspecific AK are not polyclonally activated CTL or CTL at an early stage of differentiation, but rather represent a distinct cytolytic effector system. The inclusion of HC in human MLTC may provide a useful tool for distinguishing between lysis due to the generation of specific CTL and lysis due to the generation of nonspecific AK.
D000911:Antibodies, Monoclonal / Q000502:physiology; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D004306:Dose-Response Relationship, Immunologic; D000939:Epitopes; D005910:Glioma / Q000276:immunology; D006680:HLA Antigens / Q000276:immunology; D006801:Humans; D006854:Hydrocortisone / Q000494:pharmacology*; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology*; D008213:Lymphocyte Activation / Q000187:drug effects*; D007959:Lymphocyte Culture Test, Mixed; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects / Q000276:immunology*
D000911:Antibodies, Monoclonal; D000939:Epitopes; D006680:HLA Antigens; D007166:Immunosuppressive Agents; D006854:Hydrocortisone