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

E. V. Svirshchevskaya, I. A. Sidorov, N. Y. Viskova, I. M. Dozmorov

Research output: Contribution to journalArticle

6 Scopus citations

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 × 103 to 4 × 104 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.

Original languageEnglish (US)
Pages (from-to)17-27
Number of pages11
JournalJournal of Immunological Methods
Volume159
Issue number1-2
DOIs
StatePublished - Feb 26 1993

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Keywords

  • Anti-IL-2 receptor antibody
  • CTLL-2
  • Enzyme kinetics equation
  • IL-2
  • Serum IL-2 inhibitor

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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