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Inhibition of human allergic T-helper type 2 immune responses by induced regulatory T cells requires the combination of interleukin-10-treated dendritic cells and transforming growth factor-β for their induction

Authors


Correspondence:
Dr Iris Bellinghausen, Universitäts-Hautklinik, Langenbeckstraße 1, D-55131 Mainz, Germany.
E-mail: bellinghausen@hautklinik.klinik.uni-mainz.de

Summary

Background In grass pollen-allergic individuals, T cell anergy can be induced by IL-10-treated dendritic cells (IL-10-DC) resulting in the suppression of T helper type 1 (Th1) as well as Th2 cells. This study was performed to analyse whether such IL-10-DC-treated T cells are able to act as regulatory T cells (Treg) suppressing the function of other T cells in the periphery. As transforming growth factor (TGF)-β is also a potential inducer of Treg, we additionally analysed the inhibitory capacity of TGF-β-treated T cells in this system.

Materials and Methods Freshly isolated CD4+ or CD4+CD25 T cells from grass pollen-allergic donors were stimulated with autologous mature monocyte-derived allergen-pulsed DC in the presence or absence of T cells previously cultured with IL-10-DC- and/or TGF-β.

Results Anergic T cells induced by allergen-pulsed IL-10-treated DC or allergen-pulsed DC and TGF-β enhanced IL-10 production and strongly inhibited IFN-γ production of freshly prepared peripheral CD4+ or CD4+CD25 T cells while proliferation and Th2 cytokine production were only slightly reduced. The combination of allergen-pulsed IL-10-treated DC and TGF-β had an additional effect leading to a significant suppression also of Th2 cytokine production and proliferation. Suppression was not antigen-specific and was mainly mediated by cell-to-cell contact and by the molecule-programmed death-1 and only partially by CTLA-4, TGF-β and IL-10.

Conclusion These data demonstrate that regulatory T cells that also suppress Th2 cytokine production are induced by two signals: TGF-β and IL-10-DC. This is of importance for the regulation of allergic immune responses and might be exploited for future therapeutic strategies for allergic diseases.

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