Sustained T-bet expression confers polarized human TH2 cells with TH1-like cytokine production and migratory capacities.
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Lametschwandtner, Guenther, Biedermann, Tilo, Schwaerzler, Christoph, Gunther, Claudia, kund, julia, Fassl, Sandra, Hinteregger, Sonja, Carballido-Perrig, Nicole, Szabo, Susanne, Glimcher, Laurie and Carballido, Jose (2004) Sustained T-bet expression confers polarized human TH2 cells with TH1-like cytokine production and migratory capacities. The Journal of Allergy and Clinical Immunology, 113 (5). pp. 987-994. ISSN 0091-6749
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. CONCLUSION: 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.
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| Date Deposited: | 14 Dec 2009 14:06 |
| Last Modified: | 31 Jan 2013 01:31 |
| URI: | https://oak.novartis.com/id/eprint/58 |