Heterogeneity of lymphokine-activated killer cells induced by IL-2. Separate lymphoid subpopulations lyse tumor, allogeneic blasts, and modified syngeneic blasts.
Murine splenocytes incubated for 3 to 4 days with the lymphokine, IL-2, acquire the ability to mediate the lysis of a wide variety of fresh tumor targets in short term chromium release assays. We undertook these studies to examine the lysis of splenocyte blasts by these lymphokine-activated killer (LAK) cells, to help gain an understanding of the mechanisms of target cell recognition. Allogeneic blast targets but not syngeneic blasts are highly lysable by LAK effector cells. By using congenic mice, we have shown that only the H-2 haplotype, and not other differences, determines the recognition and lysis of a blast target cell. Both Con A- and LPS-induced allogeneic splenocyte blasts are lysed and thus lectin-induced binding of effectors and targets is unlikely to be responsible for this effect. By using in vivo antibody depletion experiments, we showed that different populations of effector cells mediate the lysis of tumor cells and allogeneic blasts. Furthermore, we observed that the lysis of a susceptible blast can be inhibited only by like cold blasts of the same haplotype. These results suggest that there is a separate population of LAK cells responsible for the lysis of each type of blast target cell. Though syngeneic blasts were not lysed by LAK cells, TNP modification of syngeneic blasts converted them into cells that were recognized and lysed by LAK cells. In cold target inhibition studies, the lysis of fresh syngeneic tumor was not inhibited by TNP-modified syngeneic blasts. Similarly, the lysis of TNP-modified syngeneic blasts was not inhibited by fresh tumor. By using in vitro antibody depletion, we determined that TNP-modified blasts are lysed by LAK cells with Thy-1+ precursors, in distinction to the Thy-1- precursors involved in tumor cell lysis. Elimination of the Thy-1+ cells at the precursor stage completely abrogated the lysis of blasts but did not diminish the lysis of tumor cells. We conclude that IL-2 promotes the growth of numerous populations of effector cells with Thy-1+ precursors that have a narrow range of specificity, in contrast to the broad lytic ability for fresh tumor mediated by LAK cells with Thy-1- precursors.
LeFor
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Surgery Branch, National Cancer Institute, Bethesda, MD 20892.
Eisenthal
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Rosenberg
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D000818:Animals; D002460:Cell Line; D003208:Concanavalin A / Q000494:pharmacology; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D005260:Female; D006183:H-2 Antigens / Q000235:genetics* / Q000276:immunology; D007376:Interleukin-2 / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000145:classification* / Q000276:immunology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D013154:Spleen / Q000166:cytology; D014301:Trinitrobenzenes / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000276:immunology*
D006183:H-2 Antigens; D007376:Interleukin-2; D008070:Lipopolysaccharides; D014301:Trinitrobenzenes; D003208:Concanavalin A