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Blood, 1 April 2004, Vol. 103, No. 7, pp. 2668-2676.
Prepublished online as a Blood First Edition Paper on November 20, 2003; DOI 10.1182/blood-2003-01-0286.

Submitted January 30, 2003
Accepted November 5, 2003
Dendritic cell differentiation potential of mouse monocytes: monocytes represent immediate precursors of CD8- and CD8+ splenic dendritic cells
Beatriz Leon, Gloria Martinez del Hoyo, Veronica Parrillas, Hector Hernandez Vargas, Paloma Sanchez-Mateos, Natividad Longo, Maria Lopez-Bravo, and Carlos Ardavin*
Department of Cell Biology, Complutense University, Faculty of Biology, Madrid, Spain
Servicio de Inmunologia, Hospital Gregorio Maranon, Madrid, Spain
* Corresponding author; email: ardavin{at}bio.ucm.es.
The monocyte capacity to differentiate into dendritic cells (DCs) was originally demonstrated by human in vitro DC differentiation assays, that have subsequently become the essential methodological approach for the production of DCs to be used in DC-mediated cancer immunotherapy protocols. In addition, in vitro DC generation from monocytes is a powerful tool to study DC differentiation and maturation. However, whether DC differentiation from monocytes occurs in vivo remains controversial, and the physiological counterparts of in vitro monocyte-derived DCs are unknown. Besides, the information on murine monocytes and monocyte-derived DCs is scarce. Here we show that mouse bone marrow monocytes can be differentiated in vitro into DCs using similar conditions than those defined in humans, including in vitro cultures with GM-CSF and IL-4, and reverse transendothelial migration assays. Importantly, we demonstrate that after in vivo transfer monocytes generate CD8- and CD8+ DCs in the spleen, but differentiate into macrophages upon migration to the thoracic cavity. In conclusion, we support the hypothesis that monocytes generate DCs not only upon enter into the lymph and migration to the lymph nodes as proposed, but also upon extravasation from blood and homing to the spleen, suggesting that monocytes represent immediate precursors of lymphoid organ DCs.

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