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Human Monocyte, Lymphocyte, and Granulocyte Antibody-Dependent Cell-Mediated Cytotoxicity Toward Tumor Cells

I. General Characteristics of Cytolysis¹

From the Division of Hematology and Oncology, Ohio State University College of Medicine, Columbus, Ohio 43210, and the Simpson Memorial Research Institute, University of Michigan Medical Center, Ann Arbor, Michigan 48109

Abstract

Previous investigations of antibody-dependent cell-mediated cytotoxicity (ADCC) by human leukocytes indicated that lymphocytes and granulocytes, but not monocytes, lysed tumor cell targets. We have recently shown that monocytes, too, can carry out ADCC toward at least three allogeneic tumor cell lines. This paper examines the characteristics of ADCC by all three Fc receptor-bearing human leukocytes (monocytes, lymphocytes, and granulocytes) toward the same antibody-coated ⁵¹Cr-labeled tumor target cells. For each leukocyte effector, ADCC was found to be temperature dependent and rapid, with most target cell lysis occurring within 4 hr of incubation. The extent of target cell destruction was positively related to the effector cell/target cell ratio and to the degree of antibody sensitization of the target cells. ADCC was clearly antibody dependent since the cytotoxic event did not involve nonantibody-coated "innocent bystander" target cells and was inhibited by staphylococcal Protein A and nonspecific monomeric immunoglobulin. Granulocyte ADCC required considerably larger amounts of target cell-bound antibody than did ADCC by lymphocytes and monocytes. Conversely, larger amounts of monomeric immunoglobulin were required to inhibit granulocyte ADCC as compared to monocyte and lymphocyte ADCC in experiments utilizing identical antibody-coated target cells. In innocent by-stander experiments, no evidence for a soluble mediator of target cell lysis was found for any of the effector leukocytes. We suggest that this experimental system which involves three Fc receptor-bearing human leukocyte populations and identical antibody-coated target cell preparations provides a new and unique method for studying this cell-mediated cytotoxic event.

Footnotes

¹ This work was supported by National Cancer Institute Contract NO-2-CB-53936 and American Cancer Society Grant IM-109.

² George M. Shaw was supported by the Roessler Foundation and a fellowship from the Pharmaceutical Manufacturers Association.

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