Regulation of antigen-induced human T-lymphocyte responses by calcineurin antagonists

Sarah E. Pacocha, Alfonso Oriente, Shau Ku Huang, David M. Essayan

Research output: Contribution to journalArticle

Abstract

Background: Cyclosporin A (CS) and tacrolimus (FK506, FK) are calcineurin antagonists used widely as T-cell immunosuppressants; however, their relative efficacy on antigen-stimulated T-cell subsets remains undefined. Objective: We have examined the effects of CS and FK on antigen-driven proliferation and cytokine generation from human PBMCs and T-cell clones. Methods: Proliferation was assessed by tritiated thymidine incorporation. Cytokine generation was assessed by reverse transcription-PCR and ELISA. Results: Ragweed- and tetanus toxoid-driven proliferation of PBMCs was down-regulated equally by CS or FK. Gene expression for proinflammatory cytokines (IL-4, IL-5, IL-13, and IFN-γ) assessed by reverse transcription-PCR was down-regulated in a concentration-dependent manner by either drug. Antigen-induced proliferation of ragweed-specific Th0, Th1, or Th2 clones was inhibited by either CS or FK. Cytokine gene expression and protein secretion into culture supernatants (IL-4, IL-5, IL-13, and IFN-γ) were down-regulated in a concentration-dependent manner by either CS or FK in all relevant T-cell subsets. Interestingly, down-regulation of IL-5 protein generation from Th0 and Th2 clones was consistently less sensitive to either drug than was the effect on either IL-4 or IL-13 protein generation. Conclusion: CS and FK promote equivalent down-regulation of Th0, Th1, and Th2 responses; however, IL-5 generation is relatively insensitive to the immunomodulatory effects of calcineurin antagonists.

Original languageEnglish (US)
Pages (from-to)828-835
Number of pages8
JournalJournal of Allergy and Clinical Immunology
Volume104
Issue number4 I
StatePublished - Dec 1 1999

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Keywords

  • Cydosporine, tacrolimus
  • Human
  • IFN-γ
  • IL-13
  • IL-4
  • IL-5
  • T lymphocyte

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Pacocha, S. E., Oriente, A., Huang, S. K., & Essayan, D. M. (1999). Regulation of antigen-induced human T-lymphocyte responses by calcineurin antagonists. Journal of Allergy and Clinical Immunology, 104(4 I), 828-835.