Increased expression of the interleukin 2 (IL-2) receptor beta chain (p70) on CD56+ natural killer cells after in vivo IL-2 therapy: p70 expression does not alone predict the level of intermediate affinity IL-2 binding.
The expression of the 70-kD beta subunit of the interleukin 2 receptor (IL-2R) has been examined on peripheral blood lymphocytes (PBL) obtained from patients receiving systemic infusions of IL-2. Using monoclonal antibodies directed against p70, flow cytometric analyses revealed a greater than threefold increase in expression of the IL-2R beta chain on CD56+ natural killer (NK) cells from post-IL-2 therapy PBL relative to pre-therapy cells. The level of p70 expression on the post-therapy cells was three- to fourfold greater (based on fluorescence intensity) than the level of p70 expression on YT cells, an NK-like cell line that expresses approximately 12,000 intermediate affinity IL-2 binding sites/cell. Despite the high level of p70 expression, in 125I-IL-2 binding assays only 790-1,290 intermediate affinity IL-2 binding sites/cell were detected on post-therapy cells from six patients. These data represent the first report of increased p70 expression after in vivo IL-2 administration and suggest a requirement for at least one additional subunit for the formation of functional intermediate affinity IL-2Rs. Furthermore, the presence on the surface of post-therapy NK cells of excess p70 that does not bind IL-2 with intermediate affinity implies that the formation of intermediate affinity IL-2Rs is not solely determined by the level of p70 expression, and that the response of NK cells to IL-2 might be regulated by altering the expression of p70 or some other IL-2R subunit.
Department of Human Oncology, University of Wisconsin, Madison 53792.
S D
SD
Voss
R J
RJ
Robb
G
G
Weil-Hillman
J A
JA
Hank
K
K
Sugamura
M
M
Tsudo
P M
PM
Sondel
D000911:Antibodies, Monoclonal / Q000378:metabolism; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis*; D001667:Binding, Competitive; D001710:Biotin; D019002:CD56 Antigen; D005434:Flow Cytometry; D006801:Humans; D007376:Interleukin-2 / Q000378:metabolism* / Q000494:pharmacology / Q000627:therapeutic use; D007694:Killer Cells, Natural / Q000276:immunology*; D008213:Lymphocyte Activation / Q000187:drug effects; D011233:Precipitin Tests; D011961:Receptors, Fc / Q000502:physiology; D015375:Receptors, Interleukin-2 / Q000032:analysis* / Q000276:immunology
D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D019002:CD56 Antigen; D007376:Interleukin-2; D011961:Receptors, Fc; D015375:Receptors, Interleukin-2; D001710:Biotin