MIP-3α and MIP-1α rapidly mobilize dendritic cell precursors into the peripheral blood

Acquisition of dendritic cells (DCs) or DC precursors in vitro is critical for DC-based immunotherapy. We reported previously that administration of MIP-1 alpha mobilized a population of F4/80(-)B220(-)CD11c(+) DC precursors into peripheral blood by the expression of CCR1 and CCR5. In this study, we identified a new subset of CCR6(+) CCR1(-) CCR5(-)B220(-)CD11c(+) cells in MIP-1 alpha-administered mice. When cultured with GM-CSF, IL-4, and TNF-alpha, these cells differentiated into mature DCs, possessing the typical morphologic characteristics, phenotypes, and antigenpresenting function (termed CCR6(+) DC precursors). Although it did not directly drive the CCR6(+) DC precursors, MIP-1 alpha could recruit a population of F4/80(+)CD11c(-) monocyte/ macrophage-producing MIP-3 alpha in the peripheral blood to mobilize a CCR6(+) DC precursor subset of B220(-) CD11c(+) DC precursors. Importantly, exogenous administration of MIP-3 alpha significantly enhanced MIP-1 alpha-induced mobilization of DC precursors. Moreover, these MIP-3 alpha- and MIP-1 alpha-mobilized DC precursors could be prepared for a DC vaccine capable of eliciting CTL responses to tumor cells, leading to tumor rejection in vitro and in vivo. Taken together, this study further demonstrates the mechanism of DC precursor mobilization induced by MIP-1 alpha; that is, besides mobilizing DC precursors with CCR1 and CCR5 expressions, MIP-1 alpha recruited F4/80(+) CD11c(+) monocyte/ macrophageproducing MIP-3 alpha, which finally mobilized the CCR6(+) DC precursor subset to amplify the B220(-) CD11c(+) DC precursor population. Furthermore, combined administration of MIP-3 alpha and MIP-1 alpha may be an efficient strategy for collecting a large number of DCs appropriate for immunotherapy. J. Leukoc. Biol. 84: 1549-1556; 2008.