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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 J+Cell+Mol+Med
2008 ; 12
(2
): 690-700
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Immunosuppression induced by immature dendritic cells is mediated by
TGF-beta/IL-10 double-positive CD4+ regulatory T cells
#MMPMID18419605
Cools N
; Van Tendeloo VF
; Smits EL
; Lenjou M
; Nijs G
; Van Bockstaele DR
; Berneman ZN
; Ponsaerts P
J Cell Mol Med
2008[Apr]; 12
(2
): 690-700
PMID18419605
show ga
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)-beta 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-beta 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-beta(+)/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-beta(+)/IL-10(+) T
cells are expanded by DC independent of their maturation status, but their
suppressive function is dependent on immaturity of DC.