AI Article Synopsis
- Dendritic cells (DCs) play a crucial role in activating and regulating adaptive immune responses against infections, but current vaccination methods using DCs are limited by the availability of enough cells.
- Researchers successfully expanded and differentiated lineage-depleted murine hematopoietic stem cells into functional DCs by using HOXB4, which allows for a sustainable source of these immune cells.
- The modified DCs not only displayed key immune markers but also effectively presented antigens to T-cells and could generate specific T-cell responses in vivo, suggesting their potential for scientific and clinical applications in immunotherapy.
Article Abstract
Dendritic cells (DCs) are essential for the generation and modulation of cell-mediated adaptive immunity against infections. DC-based vaccination involves transplantation of ex vivo-generated DCs loaded with antigen in vitro, but remains limited by the number of autologous or allogeneic cells. While in vitro expansion and differentiation of hematopoietic stem cells (HSCs) into DCs seems to be the most viable alternative to overcome this problem, the complexity of HSC expansion in vitro has posed significant limitations for clinical application. We immortalized lineage-depleted murine hematopoietic bone marrow (lin(-)BM) cells with HOXB4, and differentiated them into CD11c(+)MHCII(+) DCs. These cells showed the typical DC phenotype and upregulated surface expression of co-stimulatory molecules on stimulation with various toll-like receptor ligands. These DCs efficiently presented exogenous antigen to T-cells via major histocompatibility complex (MHC) I and II and viral antigen on infection. Finally, they showed migratory capacity and were able to generate antigen-specific primed T-cells in vivo. In summary, we provide evidence that HOXB4-transduced lin(-)BM cells can serve as a viable means of generating fully functional DCs for scientific and therapeutic applications.
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| http://dx.doi.org/10.1258/ebm.2011.011140 | DOI Listing |
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