Interleukin 2-activated large granular lymphocytes: cytotoxic efficiency and mechanism of killing of tumor cell lines.
We have compared the effects of interleukin 2 (IL-2) on the proliferative and cytolytic activity of human peripheral blood lymphocytes (PBL) and natural killer (NK) cell-enriched large granular lymphocyte (LGL) subpopulations. Both populations displayed enhanced cytolytic activity against various cell lines following culture with IL-2; the killing capacity and growth of IL-2 activated LGL was, however, superior to that of PBL. Analysis of the mechanisms of action of IL-2 indicated that the percentage of cells binding to tumor targets as well as the frequency of killer cells in both lymphocyte populations was increased after culture with IL-2; however, the LGL displayed 1.5-2.5-fold greater increase in all parameters of cytotoxicity. Additionally, the rate of tumor cell killing and the recycling capacity of LGL were substantially increased (63-76-fold and 4-9-fold, respectively), following IL-2 activation. These data indicate that IL-2-induced potentiation of cytolytic activity is due to an increase in all parameters of the lytic process, and suggest that NK-enriched LGL may be a more powerful antitumor effector population for use in adoptive therapy.
Savary
C A
CA
Department of General Surgery, University of Texas, M.D. Anderson Cancer Center, Houston 77030.
Lotzová
E
E
Klostergaard
J
J
D002460:Cell Line; D002478:Cells, Cultured; D003601:Cytotoxicity Tests, Immunologic; D003602:Cytotoxicity, Immunologic; D005455:Fluorescent Antibody Technique; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008214:Lymphocytes / Q000276:immunology*; D014407:Tumor Cells, Cultured / Q000276:immunology*
D007376:Interleukin-2