title: Sustained T-bet expression confers polarized human TH2 cells with TH1-like cytokine production and migratory capacities.
abstract: BACKGROUND
  The transcription factor T-bet mediates IFN-gamma production by T(H)1 cells and suppresses T(H)2 cytokine production when ectopically expressed in polarized murine T(H)2 cells. Thus T-bet-mediated inhibition of T(H)2 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 T(H)2 cells obtained from skin biopsy specimens of patients with atopic dermatitis.
  
  
  METHODS
  The cytokine production of T(H)2 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 T(H)2 cells induced high levels of IFN-gamma and suppressed IL-5, but IL-2 and IL-4 production remained unchanged. T-bet transfection also induced IL-12Rbeta2 and CXCR3 expression on human T(H)2 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 T(H)2 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(H)1-like profile.
  
  
  CONCLUSIONS
  The combined switch in cytokine pattern and migratory potential of highly polarized human T(H)2 cells mediated by T-bet might provide an additional advantage for the treatment of allergic diseases.
authors.affiliation: Novartis Institute for Biomedical Research-Vienna, Brunnerstrasse 59, A-1235 Vienna, Austria.
authors.forename: Günther
authors.initials: G
authors.lastname: Lametschwandtner
authors.forename: Tilo
authors.initials: T
authors.lastname: Biedermann
authors.forename: Christoph
authors.initials: C
authors.lastname: Schwärzler
authors.forename: Claudia
authors.initials: C
authors.lastname: Günther
authors.forename: Julia
authors.initials: J
authors.lastname: Kund
authors.forename: Sandra
authors.initials: S
authors.lastname: Fassl
authors.forename: Sonja
authors.initials: S
authors.lastname: Hinteregger
authors.forename: Nicole
authors.initials: N
authors.lastname: Carballido-Perrig
authors.forename: Susanne J
authors.initials: SJ
authors.lastname: Szabo
authors.forename: Laurie H
authors.initials: LH
authors.lastname: Glimcher
authors.forename: José M
authors.initials: JM
authors.lastname: Carballido
mesh_terms: D002465:Cell Movement; D016207:Cytokines / Q000096:biosynthesis*; D003876:Dermatitis, Atopic / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D015870:Gene Expression; D006801:Humans; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000096:biosynthesis; D053727:Interleukin-18 Receptor alpha Subunit; D015847:Interleukin-4 / Q000096:biosynthesis; D015848:Interleukin-5 / Q000096:biosynthesis; D020411:Oligonucleotide Array Sequence Analysis; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine / Q000096:biosynthesis; D018123:Receptors, Interleukin / Q000096:biosynthesis; D053707:Receptors, Interleukin-12; D053724:Receptors, Interleukin-18; D020825:T-Box Domain Proteins; D018417:Th1 Cells / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D014157:Transcription Factors / Q000235:genetics*; D014162:Transfection; D000098815:T-bet Transcription Factor
chemical_list: C515187:CXCR3 protein, human; D016207:Cytokines; C508572:IL18R1 protein, human; D053727:Interleukin-18 Receptor alpha Subunit; D015848:Interleukin-5; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine; D018123:Receptors, Interleukin; D053707:Receptors, Interleukin-12; D053724:Receptors, Interleukin-18; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; D014157:Transcription Factors; D015847:Interleukin-4; D007371:Interferon-gamma