The specificity of lymphokine-activated killer (LAK) cells in vitro: fresh normal murine tissues are resistant to LAK-mediated lysis.
We have previously reported that murine splenocytes incubated in the lymphokine interleukin-2 acquire the ability to mediate the lysis of a variety of fresh tumor cells in short-term chromium-51 release assays. This study was designed to evaluate the effect of lymphokine-activated killer (LAK) cells on fresh normal murine tissues. The susceptibility to lysis by LAK cells of single cell suspensions from a variety of murine tissues including lung, kidney, bone marrow, peripheral blood mononuclear cells, intestinal mucosa, liver, and fetus was studied. While kidney, intestinal mucosa, and peripheral blood mononuclear cells were clearly not lysed, there was a very low level of lysis of lung, bone marrow, liver, and fetus in repeated experiments. Separation of the cell suspensions of lung and bone marrow demonstrated much higher lysis of the adherent cell population, corresponding to an increased number of macrophages in the target cell suspension. Macrophages represent a population of cells particularly sensitive to lysis by LAK cells. All of the normal tissues were highly lysable by LAK cells in antibody-dependent cellular cytotoxicity assays in the presence of the appropriate anti-H-2 antibody. In a series of cold target inhibition studies, fresh normal murine kidney, lung, and bone marrow did not inhibit the lysis of the LAK-sensitive tumor target MCA-102, further demonstrating that fresh normal tissues share little if any of the determinant recognized by LAK cells on tumor targets. However, the MCA-105 and MCA-106 tumors, and the YAC cell line, all of which are sensitive to LAK cell lysis, did inhibit the lysis of MCA-102 tumor. These studies suggest that a common determinant is present on LAK-sensitive tissues that is absent or present in very low amounts on fresh normal tissues.
Lefor
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Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892.
Rosenberg
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SA
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D000951:Antigens, Neoplasm / Q000276:immunology; D002448:Cell Adhesion; D002860:Chromium Radioisotopes / Q000378:metabolism; D003602:Cytotoxicity, Immunologic; D005260:Female; D006183:H-2 Antigens / Q000276:immunology; D007376:Interleukin-2 / Q000494:pharmacology; D007413:Intestinal Mucosa / Q000276:immunology; D007668:Kidney / Q000276:immunology; D015979:Killer Cells, Lymphokine-Activated / Q000276:immunology*; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008168:Lung / Q000276:immunology; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D011994:Recombinant Proteins / Q000494:pharmacology; D012513:Sarcoma, Experimental / Q000276:immunology; D013154:Spleen / Q000166:cytology
D000906:Antibodies; D000951:Antigens, Neoplasm; D002860:Chromium Radioisotopes; D006183:H-2 Antigens; D007376:Interleukin-2; D011994:Recombinant Proteins