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

13 Citations (Scopus)

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
Pages (from-to)828-835
Number of pages8
JournalJournal of Allergy and Clinical Immunology
Volume104
Issue number4 I
Publication statusPublished - Dec 1 1999
Externally publishedYes

Fingerprint

Cyclosporine
Interleukin-5
T-Lymphocytes
Antigens
Interleukin-13
Interleukin-4
Cytokines
Ambrosia
Clone Cells
T-Lymphocyte Subsets
Tacrolimus
Reverse Transcription
Down-Regulation
Gene Expression
Polymerase Chain Reaction
Tetanus Toxoid
Proteins
Immunosuppressive Agents
Pharmaceutical Preparations
Thymidine

Keywords

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

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Regulation of antigen-induced human T-lymphocyte responses by calcineurin antagonists. / Pacocha, Sarah E.; Oriente, Alfonso; Huang, Shau Ku; Essayan, David M.

In: Journal of Allergy and Clinical Immunology, Vol. 104, No. 4 I, 01.12.1999, p. 828-835.

Research output: Contribution to journalArticle

Pacocha, Sarah E. ; Oriente, Alfonso ; Huang, Shau Ku ; Essayan, David M. / Regulation of antigen-induced human T-lymphocyte responses by calcineurin antagonists. In: Journal of Allergy and Clinical Immunology. 1999 ; Vol. 104, No. 4 I. pp. 828-835.
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