Sustained T-bet expression confers polarized human TH2 cells with TH1-like cytokine production and migratory capacities

Günther Lametschwandtner, Tilo Biedermann, Christoph Schwärzler, Claudia Günther, Julia Kund, Sandra Fassl, Sonja Hinteregger, Nicole Carballido-Perrig, Susanne J. Szabo, Laune H. Glimcher, José M. Carballido

Research output: Contribution to journalArticlepeer-review

62 Scopus citations

Abstract

Background: The transcription factor T-bet mediates IFN-γ production by TH1 cells and suppresses TH2 cytokine production when ectopically expressed in polarized murine TH2 cells. Thus T-bet - mediated inhibition of TH2 cytokine production might be beneficial for the treatment of allergic diseases like asthma or atopic dermatitis. Objective: We sought to investigate the effects of ectopic T-bet expression in highly polarized human TH2 cells obtained from skin biopsy specimens of patients with atopic dermatitis. Methods: The cytokine production of T H2 cells retrovirally transfected with a vector expressing human T-bet was determined by means of intracellular FACS staining and ELISA. The effects of T-bet transfection were analyzed at the mRNA level by means of real-time PCR and DNA microarrays and confirmed by using functional chemokine response assays. Results: Transfection of T-bet into TH2 cells induced high levels of IFN-γ and suppressed IL-5, but IL-2 and IL-4 production remained unchanged. T-bet transfection also induced IL-12Rβ2 and CXCR3 expression on human TH2 cells, whereas the IL-18 receptor was only induced as a consequence of T-bet-mediated increased responsiveness to IL-12. Furthermore, sustained T-bet expression in human TH2 cells induced IL-2 production and decreased the secretion of IL-4. In addition, the chemokine receptor repertoire of these cells was changed toward a T H1-like profile. Conclusion: The combined switch in cytokine pattern and migratory potential of highly polarized human TH2 cells mediated by T-bet might provide an additional advantage for the treatment of allergic diseases.

Original languageEnglish
Pages (from-to)987-994
Number of pages8
JournalJournal of Allergy and Clinical Immunology
Volume113
Issue number5
DOIs
StatePublished - May 2004
Externally publishedYes

Keywords

  • Allergy
  • Atopic dermatitis
  • Chemokines
  • Cytokines
  • T-bet
  • T1/T2 cells

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