Appearance and phenotypic characterization of circulating Leu 19+ cells in cancer patients receiving recombinant interleukin 2.
The effects of recombinant interleukin 2 (rIL-2) therapy on peripheral blood mononuclear cells expressing the Leu 19 surface marker were evaluated in 20 cancer patients. Leu 19 is a protein with a molecular weight of 220,000 expressed on 15% of normal peripheral blood mononuclear cells and is found on a majority of cells that mediate non-major histocompatibility complex-restricted cytotoxicity. Increased relative and absolute numbers of circulating Leu 19+ cells were observed in all patients receiving rIL-2. Increases in Leu 19+ cells were due in part to the development of a subpopulation of "bright" Leu 19+ cells (Leu 19b+) that possessed a higher density of membrane Leu 19 antigen than Leu 19+ cells assayed prior to therapy. Further characterization of rIL-2 induced Leu 19+ cells by dual immunofluorescence revealed considerable phenotypic heterogeneity within this population based on the coexpression of "dim" CD8 (CD8d+), CD16, and CD2 markers. The percentage of Leu 19+ CD8d+ cells was increased during rIL-2 therapy and comprised up to 60% of all circulating Leu 19+ cells. CD16+ and CD16- subsets of Leu 19+ cells were also increased by rIL-2. The density of CD16 antigen coexpression varied inversely with the density of Leu 19. Conversely, whereas the percentage of Leu 19 cells coexpressing CD2 was also increased by rIL-2 administration, the density of CD2 antigen expression was higher on the Leu 19b+ subset of cells. The development of circulating lymphokine-activated killer activity in three patients was temporally associated with the development of increased levels of circulating Leu 19+ cells. These studies demonstrate that rIL-2 administration induces preferential increases in cells expressing the natural killer and lymphokine-activated killer cell-associated marker Leu 19 and that these increases are associated with the development of circulating lymphokine-activated killer activity. Furthermore, Leu 19+ cells are comprised of phenotypically heterogeneous subsets which undergo characteristic changes during rIL-2 administration.
D000943:Antigens, Differentiation / Q000032:analysis*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis; D018801:CD2 Antigens; D017252:CD3 Complex; D016827:CD8 Antigens; D006801:Humans; D007376:Interleukin-2 / Q000627:therapeutic use*; D007694:Killer Cells, Natural / Q000276:immunology; D009369:Neoplasms / Q000276:immunology / Q000628:therapy*; D010641:Phenotype; D011948:Receptors, Antigen, T-Cell / Q000032:analysis; D011961:Receptors, Fc / Q000032:analysis; D017452:Receptors, IgG; D011971:Receptors, Immunologic / Q000032:analysis; D011994:Recombinant Proteins / Q000627:therapeutic use
D000943:Antigens, Differentiation; D000945:Antigens, Differentiation, T-Lymphocyte; D018801:CD2 Antigens; D017252:CD3 Complex; D016827:CD8 Antigens; D007376:Interleukin-2; D011948:Receptors, Antigen, T-Cell; D011961:Receptors, Fc; D017452:Receptors, IgG; D011971:Receptors, Immunologic; D011994:Recombinant Proteins