Monocyte-derived dendritic cells do not proliferate and are not susceptible to retroviral transduction

Dendritic cells may be generated ex vivo from CD34+ progenitor cells or per ipheral blood mononuclear cells. Initial reports suggested that monocyte-de rived dendritic cells (MoDCs) arise from a proliferating precursor and seve ral groups subsequently reported successful retroviral transduction of thes e cells, again implying that: cell division occurs. As this is of importanc e in the development of immunotherapy protocols, we investigated whether mo nocytes proliferate as they differentiate into MoDCs and also their suscept ibility to retroviral transduction. During MoDC differentiation, there was a 51 +/- 12% reduction in cell number, 98% of cells were in G(0)/G(1), no D NA synthesis was detectable and the cell cycle regulatory proteins pRb and p130 were in the hypophosphorylated forms observed in non-cycling cells. As expected from these results, MoDCs were refractory to transduction with a GALV1 pseudotyped Moloney murine leukaemia virus (MoMLV)-based retroviral v ector. In contrast. generation of DCs from purified CD34 progenitors was ac companied by rapid entry into the cell cycle and a 41.1-fold cell expansion at the end of 14d culture.