In vivo generation of human dendritic cell subsets by Flt3 ligand

Dendritic cells (DCs) represent a family of ontogenically distinct leukocyt es involved in immune response regulation. The ability of DCs to stimulate T-cell immunity has led to their use as vectors for immunotherapy vaccines. However, it is unclear whether and to what degree in vitro-generated DCs a re representative of DCs that develop in vivo. Treatment of mice with human Flt3 ligand (FL) dramatically increases the number of DCs, We report here that administration of FL to healthy human volunteers increased the number of circulating CD11c(+) IL-3R alpha(low) DC (mean 44-fold) and CD11c(+) IL- 3R alpha(high) DC precursors (mean 12-fold). Moreover, the CD11c(+) DCs wer e efficient stimulators of T cells in vitro. Thus, FL can expand the number of circulating, functionally competent human DCs in vivo. (C) 2000 by The American Society of Hematology.