Regulation of interleukin 2 receptor expression: effects of phorbol diester, phospholipase C, and reexposure to lectin or antigen

J Immunol. 1984 Dec;133(6):3054-61.

Abstract

Anti-Tac monoclonal antibody identifies the receptor for interleukin 2 (IL 2, or T cell growth factor) present on activated human T lymphocytes. By using tritiated anti-Tac, we now report a sensitive and specific binding assay to evaluate cell surface IL 2 receptor expression. IL 2 receptors on human peripheral blood lymphocytes can be detected within 6 hr after PHA stimulation. PHA-induced receptor expression is inhibited by actinomycin D and cycloheximide, but not by mitomycin C, suggesting a requirement for de novo RNA and protein synthesis, but not DNA synthesis. Scatchard analysis of [3H]-anti-Tac binding to lymphocytes stimulated with PHA for 3 days revealed from 20,000 to 60,000 molecules of antibody bound per cell, and a Kd of 1 to 3 x 10(-10) mol/l. Sequential binding studies of activated human lymphocytes maintained in long-term culture with IL 2 demonstrated a progressive decline in receptor number correlating with diminished growth rate. Restimulation with lectin or antigen increased the number of IL 2 receptors, suggesting that IL 2 dependent immune responses may be regulated, at least in part, by IL 2 receptor expression. Receptor number was also increased by PMA. Moreover, similar effects were produced by incubation with phospholipase C but not interleukin 1. Because both PMA and phospholipase C result in activation of protein kinase C, these data suggest the possibility that activation of protein kinase C may induce IL 2 receptor expression.

MeSH terms

  • Antigens, Surface / analysis
  • Antigens, Surface / immunology
  • Binding Sites, Antibody
  • Drug Synergism
  • Growth Inhibitors / pharmacology
  • Humans
  • Interleukin-1 / physiology
  • Isoantigens / immunology
  • Kinetics
  • Lymphocyte Activation / drug effects*
  • Phorbols / pharmacology*
  • Phospholipases / pharmacology*
  • Phytohemagglutinins / pharmacology
  • Receptors, Immunologic / biosynthesis
  • Receptors, Immunologic / drug effects
  • Receptors, Immunologic / metabolism*
  • Receptors, Interleukin-2
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism
  • Tetradecanoylphorbol Acetate / pharmacology*
  • Tumor Necrosis Factor Receptor Superfamily, Member 7
  • Type C Phospholipases / pharmacology*

Substances

  • Antigens, Surface
  • Growth Inhibitors
  • Interleukin-1
  • Isoantigens
  • Phorbols
  • Phytohemagglutinins
  • Receptors, Immunologic
  • Receptors, Interleukin-2
  • Tumor Necrosis Factor Receptor Superfamily, Member 7
  • Phospholipases
  • Type C Phospholipases
  • Tetradecanoylphorbol Acetate