Lysis of autologous human macrophages by lymphokine-activated killer cells: interaction of effector cell and target cell conjugates analyzed by scanning electron microscopy.
Lymphokine (i.e., interleukin 2; IL-2)-activated killer (LAK) cells derived from normal human blood are known to destroy human tumor target cells. Accordingly, immunotherapy modalities using IL-2, either alone or in combination with LAK cells, have been evaluated for eradicating metastatic cancer. In studies conducted to characterize receptors on LAK cell membrane ultrastructures, we observed that LAK cells kill autologous human monocyte-derived macrophages (M phi). In these experiments, peripheral blood mononuclear cells of a healthy adult donor were cultured to generate LAK cells and autologous non-adherent M phi. Thereafter, conjugates were prepared by incubating for 3 h autologous populations of LAK cells and M phi. Examination of the conjugates by scanning electron microscopy (SEM) identified LAK cell-mediated killing of M phi. Moreover, SEM analysis of the LAK cell membrane architecture identified microvilli-like ultrastructures that provided a physical bridge that joined together the LAK cell and M phi. The immunological mechanism(s) underling LAK cell killing of autologous M phi is not known; nevertheless, these conjugates will provide a useful model to study membrane receptors on ultrastructures that mediate the initial stages of cytolysis that include target cell recognition and cell-to-cell adhesion. The results of our observations and the findings of other investigators who have also demonstrated LAK cell killing of autologous normal human leukocytes are discussed in the context of the association of IL-2 and IL-2-activated killer cells with side effects observed in ongoing clinical trials and with autoimmune disorders.
Streck
R J
RJ
Department of Molecular Immunology, Roswell Park Memorial Institute, Buffalo, New York 14263.
Helinski
E H
EH
Ovak
G M
GM
Pauly
J L
JL
D015551:Autoimmunity; D002448:Cell Adhesion / Q000502:physiology; D002450:Cell Communication / Q000502:physiology; D002462:Cell Membrane / Q000502:physiology / Q000648:ultrastructure; D002470:Cell Survival / Q000502:physiology; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology; D015979:Killer Cells, Lymphokine-Activated / Q000502:physiology* / Q000648:ultrastructure; D008213:Lymphocyte Activation; D008264:Macrophages / Q000502:physiology* / Q000648:ultrastructure; D008855:Microscopy, Electron, Scanning; D008871:Microvilli / Q000648:ultrastructure; D013602:T-Lymphocytes, Cytotoxic
D007376:Interleukin-2