Potentiation of human natural killer cell cytotoxicity by Salmonella bacteria is an interferon- and interleukin-2-independent process that utilizes CD2 and CD18 structures in the effector phase.
Incubation of large granular lymphocytes (LGL) with glutaraldehyde-fixed bacteria stimulated in the supernatant the production of interferon (IFN), which proved to be mainly IFN-gamma. Even though IFN-gamma was produced upon exposure of LGL to bacteria, anti-IFN-gamma antibodies failed to interfere with induction of cytotoxicity by bacterial contact. Anti-IFN-gamma receptor antibodies had no effect on the induction of activated killing by bacterial contact either. We also tested the effect of anti-IFN-alpha antibody, but it failed to interfere with induction of cytotoxicity by bacterial contact. No interleukin-2 (IL-2) was detected in the culture supernatant of bacterially activated LGL by the mouse HT2 cell assay, nor did we detect any IL-2 mRNA in bacterially activated LGL by Northern RNA blot assay. Neutralizing anti-IL-2 antiserum had no effect on the induction of activated killing by bacterial contact, and recombinant IL-4 did not interfere with the induction of activated killing. We then studied the membrane structures involved in bacterially activated killing. Anti-CD18 monoclonal antibody did not interfere with the induction phase of bacterially activated killing. However, both anti-CD18 and anti-CD2 antibodies inhibited the effector phase of bacterially activated killing. The effector pathways utilized by activated LGL depended on the mode of activation in that even though bacterially activated LGL were sometimes blocked by anti-CD2 monoclonal antibody, recombinant-IL-2-stimulated LGL were not. In conclusion, our present results suggest that there may be mediators other than exogenously secreted IFNs and IL-2 which are responsible for the induction of activated killing after bacterial contact. CD18 and CD2 structures were shown to be involved in the effector phase of bacterially activated killing.
Tarkkanen
J
J
Department of Pathology, University of Helsinki, Finland.
Saksela
E
E
D000911:Antibodies, Monoclonal / Q000276:immunology; D015703:Antigens, CD / Q000276:immunology* / Q000378:metabolism; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology*; D018821:CD18 Antigens; D018801:CD2 Antigens; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic; D006801:Humans; D007372:Interferons / Q000378:metabolism*; D007376:Interleukin-2 / Q000378:metabolism*; D015847:Interleukin-4 / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology*; D008213:Lymphocyte Activation; D008222:Lymphokines / Q000502:physiology; D011971:Receptors, Immunologic / Q000276:immunology*; D011994:Recombinant Proteins / Q000378:metabolism; D012475:Salmonella / Q000276:immunology*
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D018821:CD18 Antigens; D018801:CD2 Antigens; D007376:Interleukin-2; D008222:Lymphokines; D011971:Receptors, Immunologic; D011994:Recombinant Proteins; D015847:Interleukin-4; D007372:Interferons