title: Dendritic cells derived from HOXB4-immortalized hematopoietic bone marrow cells.
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.
authors: Department for Clinical Immunology and Rheumatology, Hannover Medical School, Carl-Neuberg-Strasse 1, Hannover, Germany.
authors: Abdul Mannan
authors: AM
authors: Baru
authors: Jayendra Kumar
authors: JK
authors: Krishnaswamy
authors: Anchana
authors: A
authors: Rathinasamy
authors: Michaela
authors: M
authors: Scherr
authors: Matthias
authors: M
authors: Eder
authors: Georg M N
authors: GM
authors: Behrens
mesh_terms: D000818:Animals; D017951:Antigen Presentation; D018929:Cell Culture Techniques; D002454:Cell Differentiation; D002465:Cell Movement; D003713:Dendritic Cells / Q000166:cytology* / Q000276:immunology; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D018398:Homeodomain Proteins / Q000494:pharmacology*; D006801:Humans; D007111:Immunity, Cellular; D008024:Ligands; D008285:Major Histocompatibility Complex; D051379:Mice; D008810:Mice, Inbred C57BL; D010587:Phagocytosis; D010641:Phenotype; D013601:T-Lymphocytes / Q000502:physiology; D051193:Toll-Like Receptors / Q000378:metabolism; D014157:Transcription Factors / Q000494:pharmacology*
chemical_list: C090460:HOXB4 protein, human; D018398:Homeodomain Proteins; D008024:Ligands; D051193:Toll-Like Receptors; D014157:Transcription Factors