Open AccessImmunosuppression induced by immature dendritic cells is mediated by TGF‐β/IL‐10 double‐positive CD4 + regulatory T cells
Author(s) -
Cools N.,
Van Tendeloo V.F.I.,
Smits E.L.J.M.,
Lenjou M.,
Nijs G.,
Van Bockstaele D.R.,
Berneman Z.N.,
Ponsaerts P.
Publication year - 2008
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/j.1582-4934.2007.00084.x
Subject(s) - il 2 receptor , t cell , foxp3 , priming (agriculture) , antigen presenting cell , biology , cytotoxic t cell , cd8 , microbiology and biotechnology , interleukin 21 , cd40 , antigen , immunology , immune system , in vitro , biochemistry , botany , germination
Dendritic cells (DC) have important functions in T cell immunity and T cell tolerance. Previously, it was believed that T cell unresponsiveness induced by immature DC (iDC) is caused by the absence of inflammatory signals in steady‐state in vivo conditions and by the low expression levels of costimulatory molecules on iDC. However, a growing body of evidence now indicates that iDC can also actively maintain peripheral T cell tolerance by the induction and/or stimulation of regulatory T cell populations. In this study, we investigated the in vitro T cell stimulatory capacity of iDC and mature DC (mDC) and found that both DC types induced a significant increase in the number of transforming growth factor (TGF)‐β and interleukin (IL)‐10 double‐positive CD4 + T cells within 1 week of autologous DC/T cell co‐cultures. In iDC/T cell cultures, where antigen‐specific T cell priming was significantly reduced as compared to mDC/T cell cultures, we demonstrated that the tolerogenic effect of iDC was mediated by soluble TGF‐β and IL‐10 secreted by CD4 + CD25 − FOXP3 − T cells. In addition, the suppressive capacity of CD4 + T cells conditioned by iDC was transferable to already primed antigen‐specific CD8 + T cell cultures. In contrast, addition of CD4 + T cells conditioned by mDC to primed antigen‐specific CD8 + T cells resulted in enhanced CD8 + T cell responses, notwithstanding the presence of TGF‐β + /IL‐10 + T cells in the transferred fraction. In summary, we hypothesize that DC have an active role in inducing immunosuppressive cytokine‐secreting regulatory T cells. We show that iDC‐conditioned CD4 + T cells are globally immunosuppressive, while mDC induce globally immunostimulatory CD4 + T cells. Furthermore, TGF‐β + /IL‐10 + T cells are expanded by DC independent of their maturation status, but their suppressive function is dependent on immaturity of DC.