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Dendritic Cells and B Cells Cooperate in the Generation of CD4+ CD25+ FOXP3+ Allogeneic T Cells

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2010
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Moore, C.
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Dendritic Cells and B Cells Cooperate in the Generation of CD4+ CD25+ FOXP3+ Allogeneic T Cells
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Author
  • Moore, C.;
  • Sauma Mahaluf, Daniela;
  • Reyes Pérez, P. A.;
  • Morales Peña, José;
  • Rosemblatt Silber, Mario César;
  • Bono Merino, María Rosa;
  • Fierro, J. A.;
Abstract
Background. CD4 CD25 Foxp3 regulatory T cells (Treg) play an essential role in immune tolerance, suppressing responses against self-antigens. Additionally, Treg play an important role in maintaining immunosuppression to alloantigens as well as to other antigens. It is well known that in the gut, a subset of dendritic cells produces retinoic acid (RA), which together with transforming growth factor (TGF- ) is able to differentiate naïve T cells into Treg. The aim of this study was to establish the role of antigen-presenting cells (APC) in the differentiation of allogeneic Tregs under the effect of RA and TGF- . Methods. Splenic CD4 CD25 naïve T cells from C57BL/6 mice were co-cultured with splenic CD11c-enriched APC from Balb/c mice in the presence of TGF- , RA, and interleukin (IL-2). After 6 days of culture, cells were analyzed for the expression of Foxp3 by flow cytometry. Additionally, we investigated the role of B cells and dendritic cells (DCs) and their stimulatory capacity in the generation of Tregs. Results. Our results showed that co-culture of naive T cells with the appropriate level of stimulation by APC in the presence of TGF- , RA, and IL-2 provided a new powerful approach to generate allogeneic Treg cells. We demonstrated that although B cells and DCs can generate Tregs by themselves, a mixure of both APC improved their capacity to efficiently generate Tregs. Also, we observed that although the addition of IL-2 to the cultures was not crucial to generate Tregs, it was required to optimize their expansion and cell survival.
Patrocinador
Supported by FONDECYT grants 1060834, 1060253, 1080416 Universidad Andres Bello grant DI-08-08/I and PFB-16 fron CONICYT, Chile.
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URI: https://repositorio.uchile.cl/handle/2250/119053
DOI: doi:10.1016/j.transproceed.2009.12.044
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Transplantation Proceedings, 42, 371–375 (2010)
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