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-beta for their induction.
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)-beta is also a potential inducer of Treg, we additionally analysed the inhibitory capacity of TGF-beta-treated T cells in this system.


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-beta.


RESULTS
Anergic T cells induced by allergen-pulsed IL-10-treated DC or allergen-pulsed DC and TGF-beta enhanced IL-10 production and strongly inhibited IFN-gamma 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-beta 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-beta and IL-10.


CONCLUSIONS
These data demonstrate that regulatory T cells that also suppress Th2 cytokine production are induced by two signals: TGF-beta 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.
Bellinghausen
I
I
Department of Dermatology, University of Mainz, Mainz, Germany.
König
B
B
Böttcher
I
I
Knop
J
J
Saloga
J
J
D000485:Allergens / Q000276:immunology; D015703:Antigens, CD / Q000276:immunology; D000943:Antigens, Differentiation / Q000276:immunology; D060908:CTLA-4 Antigen; D002450:Cell Communication; D049109:Cell Proliferation; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology*; D007114:Immunization; D007371:Interferon-gamma / Q000276:immunology; D016753:Interleukin-10 / Q000276:immunology*; D015847:Interleukin-4 / Q000276:immunology; D015848:Interleukin-5 / Q000276:immunology; D006109:Poaceae; D011058:Pollen; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000276:immunology / Q000494:pharmacology*
D000485:Allergens; D015703:Antigens, CD; D000943:Antigens, Differentiation; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D015848:Interleukin-5; D016212:Transforming Growth Factor beta; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma