Effect of interferon-γ, interleukin-2 and interleukin-4 on cyclosporin-a-mediated inhibition of anti-CD3-induced T-lymphocyte proliferation

L. Fitzpatrick, M. Kaiser, B. H. Stewart, D. W. Hoskin

Research output: Contribution to journalArticlepeer-review

5 Citations (Scopus)

Abstract

It is generally believed that cyclosporin A (CsA) inhibits T-cell activation largely by blocking interleukin (IL)-2 production, although CsA also inhibits the secretion of other growth-promoting lymphokines. To investigate the importance of downregulated synthesis of IL-4 and interferon (IFN)-γ, in addition to IL-2, in CsA-mediated inhibition of T-lymphocyte proliferation, exogenous IL-2, IL-4, and IFN-γ were added to murine T-cells stimulated with anti-CD3 monoclonal antibody in the presence of an inhibitory concentration of CsA. Either IL-2 or IL-4 alone were able to partially counteract the inhibitory effect of CsA on anti-CD3-induced T-lymphocyte proliferation, whereas IFN-γ had no discernable effect. IL-2 and IL-4, in combination, were able to largely reverse the immunosuppressive activity of CsA. These results indicate that (1) CsA fails to block T-cell signal transduction pathways coupled to IL-2 and IL-4 receptors, and (2) IL-2 and IL-4 have an additive effect in promoting the proliferation of a heterogenous T-cell population stimulated with anti-CD3 monoclonal antibody.

Original languageEnglish
Pages (from-to)289-293
Number of pages5
JournalInternational Journal of Immunopharmacology
Volume16
Issue number4
DOIs
Publication statusPublished - Apr 1994

Bibliographical note

Funding Information:
Acknowledgements -- This study was supported by a grant to D. W. H. from the Natural Sciences and Engineering Research Council of Canada. M. K. was the recipient of an NSERC postgraduate scholarship. We wish to thank Jonathan Blay for critical reading of this manuscript.

ASJC Scopus Subject Areas

  • Immunology
  • Pharmacology

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