Regulation of natural and antibody-dependent cellular cytotoxicity by staphylococcal enterotoxin A.
The capacity of staphylococcal enterotoxin A (SEA), a potent T cell mitogen and inducer of interferon-gamma (IFN-gamma), to modulate human lymphocyte cytotoxic function has been examined and compared with the influence of purified and/or gene cloned IFN-alpha. While the natural killer (NK) cell function of peripheral blood lymphocytes is significantly augmented after exposure to IFN-alpha, levels of cytotoxicity were even greater following pre-treatment with optimal concentrations (0 X 1 microgram/ml) of SEA. Moreover lymphocyte (K cell)-mediated antibody-dependent cellular cytotoxicity (ADCC), which is uninfluenced by exposure to IFN-alpha, was, in most instances, potentiated by SEA. However the efficacy with which SEA augmented natural cytotoxic function was most apparent from experiments utilizing extravascular lymphoid effectors in which basal NK activity is weak and the response to IFN-alpha variable (in the case of lymph node cells) or undetectable (in the case of tonsillar lymphocytes). Co-fractionation on Percoll gradients of lymphocytes responding to SEA with native NK cells suggested that SEA affects NK cells or their non-cytolytic precursors possibly by elaboration of soluble mediators rather than by the induction of a ligand binding mechanism analogous to lectin-dependent cytotoxicity. This system could have important implications for the regulation of NK cell function by lymphocyte stimulatory factors, particularly in lymphoid tissues where indigenous NK activity is low and relatively unaffected by IFN-alpha.
D000920:Antibody-Dependent Cell Cytotoxicity / Q000187:drug effects*; D002469:Cell Separation; D004768:Enterotoxins / Q000494:pharmacology*; D006801:Humans; D007370:Interferon Type I / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000502:physiology; D008198:Lymph Nodes / Q000166:cytology; D014066:Palatine Tonsil / Q000166:cytology; D013154:Spleen / Q000166:cytology
D004768:Enterotoxins; D007370:Interferon Type I; C026066:enterotoxin A, Staphylococcal