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10.1111/j.1582-4934.2007.00084.x

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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-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.
  • |*Immunosuppression Therapy [MESH]
  • |CD4-Positive T-Lymphocytes/*immunology [MESH]
  • |Cell Differentiation [MESH]
  • |Cells, Cultured [MESH]
  • |Coculture Techniques [MESH]
  • |Dendritic Cells/cytology/*immunology [MESH]
  • |Humans [MESH]
  • |Immunomagnetic Separation [MESH]
  • |Immunophenotyping [MESH]
  • |Interleukin-10/*immunology [MESH]
  • |Models, Immunological [MESH]
  • |Monocytes/cytology [MESH]
  • |T-Lymphocytes, Regulatory/*immunology [MESH]


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