Quantitative analysis of interleukin-2-induced proliferation in the presence of inhibitors using a mathematical model

J Immunol Methods. 1993 Feb 26;159(1-2):17-27. doi: 10.1016/0022-1759(93)90137-v.

Abstract

The proliferative response of CTLL-2 cells to human recombinant interleukin-2 (IL-2) can be modeled mathematically using enzyme kinetic equations. This approach has been used to analyze dose-response curves (IL-2 concentration vs. level of proliferation) measured by MTT and [3H]TdR assays. The values of functional dissociation constants, equivalent to IL-2 concentrations giving 50% of the maximal response, depended on the cell concentration and increased from 4 to 60 pM for the [3H]TdR assay and from 40 to 140 pM for the MTT assay when the cell concentration was increased from 2 x 10(3) to 4 x 10(4) cells/well. The types of inhibition and dissociation constants for various inhibitors of IL-2-dependent proliferation such as mAbs against IL-2 receptor (7D4 and AMT13) and normal mouse serum (NMS) were also analyzed. Both mAbs exhibited competitive mechanisms of inhibition whereas NMS inhibited IL-2-driven proliferation in a mixed manner. Two gel-filtration fractions of NMS with inhibitory activity manifested different types of inhibition: purely competitive type of inhibition in the case of a 10-15 kDa fraction and a mixed type of inhibition for a 100-150 kDa fraction. The proposed model can also be used for quantitative analysis of the influence of various factors (pH, temperature, cultivation condition) on the level of proliferation.

MeSH terms

  • Animals
  • Antibodies, Monoclonal / immunology
  • Cell Line
  • Dose-Response Relationship, Drug
  • Interleukin-2 / antagonists & inhibitors
  • Interleukin-2 / pharmacology*
  • Lymphocyte Activation / drug effects*
  • Male
  • Mathematics
  • Mice
  • Mice, Inbred C57BL
  • Models, Biological
  • Rats
  • Rats, Wistar
  • Receptors, Interleukin-2 / physiology
  • Recombinant Proteins / pharmacology
  • T-Lymphocytes, Cytotoxic / immunology*

Substances

  • Antibodies, Monoclonal
  • Interleukin-2
  • Receptors, Interleukin-2
  • Recombinant Proteins