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Sustained T-bet expression confers polarized human TH2 cells with TH1-like cytokine production and migratory capacities.
J Allergy Clin Immunol. 2004 May; 113(5):987-94.JA

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.

Authors+Show Affiliations

Novartis Institute for Biomedical Research-Vienna, Brunnerstrasse 59, A-1235 Vienna, Austria.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

15131585

Citation

Lametschwandtner, Günther, et al. "Sustained T-bet Expression Confers Polarized Human TH2 Cells With TH1-like Cytokine Production and Migratory Capacities." The Journal of Allergy and Clinical Immunology, vol. 113, no. 5, 2004, pp. 987-94.
Lametschwandtner G, Biedermann T, Schwärzler C, et al. Sustained T-bet expression confers polarized human TH2 cells with TH1-like cytokine production and migratory capacities. J Allergy Clin Immunol. 2004;113(5):987-94.
Lametschwandtner, G., Biedermann, T., Schwärzler, C., Günther, C., Kund, J., Fassl, S., Hinteregger, S., Carballido-Perrig, N., Szabo, S. J., Glimcher, L. H., & Carballido, J. M. (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), 987-94.
Lametschwandtner G, et al. Sustained T-bet Expression Confers Polarized Human TH2 Cells With TH1-like Cytokine Production and Migratory Capacities. J Allergy Clin Immunol. 2004;113(5):987-94. PubMed PMID: 15131585.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Sustained T-bet expression confers polarized human TH2 cells with TH1-like cytokine production and migratory capacities. AU - Lametschwandtner,Günther, AU - Biedermann,Tilo, AU - Schwärzler,Christoph, AU - Günther,Claudia, AU - Kund,Julia, AU - Fassl,Sandra, AU - Hinteregger,Sonja, AU - Carballido-Perrig,Nicole, AU - Szabo,Susanne J, AU - Glimcher,Laurie H, AU - Carballido,José M, PY - 2004/5/8/pubmed PY - 2004/6/18/medline PY - 2004/5/8/entrez SP - 987 EP - 94 JF - The Journal of allergy and clinical immunology JO - J Allergy Clin Immunol VL - 113 IS - 5 N2 - 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. SN - 0091-6749 UR - https://www.unboundmedicine.com/medline/citation/15131585/Sustained_T_bet_expression_confers_polarized_human_TH2_cells_with_TH1_like_cytokine_production_and_migratory_capacities_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0091674904009765 DB - PRIME DP - Unbound Medicine ER -