Sustained T-bet expression confers polarized human T_H2 cells with T_H1-like cytokine production and migratory capacities

Background: The transcription factor T-bet mediates IFN-γ production by T_H1 cells and suppresses T_H2 cytokine production when ectopically expressed in polarized murine T_H2 cells. Thus T-bet - mediated inhibition of T_H2 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_H2 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 T_H2 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 T_H2 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_H2 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 T_H2 cells mediated by T-bet might provide an additional advantage for the treatment of allergic diseases.