A kinetic analysis of the effects of interleukin-2 diphtheria toxin fusion protein upon activated T cells

Transplantation. 1990 Jan;49(1):198-201. doi: 10.1097/00007890-199001000-00044.


The interleukin-2 diphtheria toxin-related fusion protein (IL-2 toxin) inhibits protein and DNA synthesis IN rIL-2 (10(-10) M) stimulated T lymphoblasts in a dose-dependent fashion. However, prior to target cell death very low concentrations of rIL-2 and IL-2 toxin synergistically stimulate [3H] thymidine incorporation despite inhibition of [14C] leucine uptake. A sequential analysis of [3H] thymidine incorporation shows that high IL-2 toxin concentration (10(-9)-10(-7) M) stimulates DNA synthesis at 18 hr of culture and inhibits [3H] thymidine uptake after 24 hr, while low concentrations of IL-2 toxin (10(-12)-10(-10) M) exhibits stimulatory effects only after 24 hr of culture. Anti-Tac a monoclonal antibody directed against the p55 chain of the high affinity IL-2 receptor (IL-2R) blocks the stimulatory effects of high-dose IL-2 toxin, thereby proving that these effects are mediated through the IL-2 domain of the fusion protein. At 7 hr following interaction with IL-2R receptor (IL-2R)+ T cells, IL-2 toxin-treated cells evidence augmented transcription of the heat shock protein gene, an effect indistinguishable from those mediated by rIL-2. We conclude that interaction of IL-2 toxin with IL-2R+ T cells initially mimicks the stimulatory effects of IL-2 upon gene transcription and DNA synthesis yet concomitant inhibition of protein synthesis is evident.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Cells, Cultured
  • DNA / biosynthesis
  • Diphtheria Toxin / pharmacology*
  • Humans
  • Interleukin-2 / pharmacology*
  • Lymphocyte Activation
  • Protein Biosynthesis
  • Receptors, Interleukin-2 / analysis
  • Recombinant Fusion Proteins / pharmacology*
  • T-Lymphocytes / drug effects*
  • Transcription, Genetic / drug effects


  • Diphtheria Toxin
  • Interleukin-2
  • Receptors, Interleukin-2
  • Recombinant Fusion Proteins
  • DNA