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10.1111/j.1582-4934.2007.00084.x

http://scihub22266oqcxt.onion/10.1111/j.1582-4934.2007.00084.x
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C3822554!3822554!18419605
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suck abstract from ncbi


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pmid18419605      J+Cell+Mol+Med 2008 ; 12 (2): 690-700
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  • Immunosuppression induced by immature dendritic cells is mediated by TGF-?/IL-10 double-positive CD4+ regulatory T cells #MMPMID18419605
  • Cools N; Van Tendeloo V; Smits E; Lenjou M; Nijs G; Van Bockstaele D; Berneman Z; Ponsaerts P
  • J Cell Mol Med 2008[Apr]; 12 (2): 690-700 PMID18419605show 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)-? 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-? 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-?+/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-?+/IL-10+ T cells are expanded by DC independent of their maturation status, but their suppressive function is dependent on immaturity of DC.
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