Characterization of lymphokine-activated killing by human peripheral blood mononuclear cells stimulated with interleukin 2 (IL-2) analogs specific for the intermediate affinity IL-2 receptor.
Interleukin 2-stimulated human peripheral blood mononuclear cells (PBMC) generate lymphokine-activated killing (LAK). Using the IL-2 analogs R38A and F42K, which interact primarily with the beta and gamma subunits of the IL-2 receptor, we assessed the roles of IL-2R beta gamma and the high-affinity IL-2 receptor complex in LAK activation. Although the kinetics of LAK activation were identical, lytic activity was approximately 30% lower and proliferation was up to 55% lower in those PBMC stimulated by R38A or F42K than in those exposed to wild-type IL-2. The percentage of cells expressing cell-surface markers such as CD3, CD4, CD8, and CD16 was not significantly different after treatment with wild-type IL-2, R38A, or F42K; however, the proportion of cells expressing IL-2R alpha increased dramatically in response to stimulation by F42K (30%) compared to stimulation by either rIL-2 or R38A (15%). In addition, by Day 7 the concentration of soluble IL-2R alpha in analog-stimulated LAK culture supernatants was 50-75% less than that from wild-type IL-2-cultured cells. These findings suggest that interaction of IL-2 with IL-2R beta gamma alone is sufficient for both proliferation and the generation of LAK, and that stimulation with subunit-specific IL-2 analogs results in differential regulation of the IL-2R alpha on human LAK cells.
Heaton
K M
KM
Department of Tumor Biology, University of Texas M. D. Anderson Cancer Center, Houston 77030.
Ju
G
G
Morris
D K
DK
Delisio
K
K
Bailon
P
P
Grimm
E A
EA
D001667:Binding, Competitive; D002462:Cell Membrane / Q000276:immunology; D006801:Humans; D007376:Interleukin-2 / Q000031:analogs & derivatives / Q000494:pharmacology*; D015979:Killer Cells, Lymphokine-Activated / Q000276:immunology; D009000:Monocytes / Q000187:drug effects*; D015375:Receptors, Interleukin-2 / Q000737:chemistry / Q000276:immunology*; D011994:Recombinant Proteins / Q000494:pharmacology
D007376:Interleukin-2; D015375:Receptors, Interleukin-2; D011994:Recombinant Proteins