In vivo effects of recombinant IL-2. I. Isolation of circulating Leu-19+ lymphokine-activated killer effector cells from cancer patients receiving recombinant IL-2.
This study was designed to isolate and phenotypically characterize lymphokine-activated killer (LAK) cells generated in vivo during administration of high dose rIL-2 to cancer patients. The development of circulating LAK effector cells in these patients was demonstrated by the ability of fresh PBL to exhibit lytic activity against the NK-resistant Daudi cell line and fresh tumor cells without prior in vitro culture with rIL-2. Kinetic studies demonstrated that circulating LAK effector cells are detectable 4 to 6 wk after the initiation of rIL-2 therapy. Cells isolated by FACS revealed that circulating LAK cells are Leu-19+, Leu-17+ but CD5-. We have previously reported that circulating Leu-19+ cells are heterogeneous with regard to the expression of CD16 and CD8. Since sorting of cells expressing Leu-19 and either low quantities of CD8 or CD16 resulted in cytolytic activity in both the positive and negative fractions, these latter two markers do not identify subpopulations of Leu-19+ cells with or without LAK cytolytic activity. Although all LAK cells generated in vivo were Leu-19+, we generated LAK cells from the Leu-19- subpopulation after in vitro culture with rIL-2, suggesting that at least some of in vitro generated LAK cells are derived from Leu-19- precursor cells. These LAK cells did not, however, express the Leu-19 surface marker. Based on the functional data reported in this paper, we conclude that circulating LAK effector cells are a phenotypically heterogeneous population that express surface Ag in association with NK cells and not T lymphocytes.
McMannis
J D
JD
Section of Hematology/Oncology, Loyola University Stritch School of Medicine, Maywood, IL 60153.
Fisher
R I
RI
Creekmore
S P
SP
Braun
D P
DP
Harris
J E
JE
Ellis
T M
TM
D000951:Antigens, Neoplasm / Q000032:analysis; D000954:Antigens, Surface / Q000032:analysis; D002277:Carcinoma / Q000188:drug therapy* / Q000276:immunology; D002454:Cell Differentiation / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000276:immunology; D003601:Cytotoxicity Tests, Immunologic; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology* / Q000627:therapeutic use; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000276:immunology; D008545:Melanoma / Q000188:drug therapy* / Q000276:immunology; D010641:Phenotype; D011994:Recombinant Proteins / Q000494:pharmacology / Q000627:therapeutic use
D000951:Antigens, Neoplasm; D000954:Antigens, Surface; D007376:Interleukin-2; D011994:Recombinant Proteins