Flt3 ligand expands dendritic cell numbers in normal and malignant murineprostate

We have developed a murine model that facilitates the structuraland functional analysis in vivo of dendritic cell (DC)-mediatedphagocytosis of prostate epithelial cells. Recombinant human Flt3ligand (rhFL) expands the number of dendritic cells in lymphoidand non-lymphoid tissues of mice. We show that rhFL also inducedthe ingress of dendritic cells into murine prostate, which involutesvia epithelial apoptosis after surgical castration. Intact or castratedC57BL/6 and syngeneic transgenic adenocarcinoma of mouseprostate (TRAMP) mice were treated with rhFL or PBS control. Prostateand spleen were then studied by flow cytometry and immunohistochemistry.The number of prostatic CD11c(+) and CD11b(+) dendriticcells increased significantly in rhFL-treated mice compared withPBS-treated control mice and this effect was greatly augmented bycastration of the mice. The immunophenotype of rhFL-mobilized prostaticcells was consistent with that of Langerhans cells (MHC class II+ , CD11c(+) ,CD11b(+) , DEC-205(+) , CD8alpha(-) ).MHC class II+ and CD11c(+) dendriticcells that were present in the prostate glands of rhFL-treated andcastrated C57BL/6 mice were intimately associated withTUNEL(+) inclusions, which suggests that Langerhans-typedendritic cells in prostate participated in the clearance of apoptoticcells. Expression of MHC class II, CD54, CD80 and CD86 by prostaticdendritic cells was not up-regulated after castration and freshlyisolated rhFL-induced prostate cells were unable to prime allogeneicT cells unless they were activated by culture either on plasticor with recombinant soluble CD40 ligand. Our data suggest that rhFL-mobilizedprostatic dendritic cells resemble the functionally immature dendriticcells, which reside in peripheral tissues and contribute to themaintenance of peripheral tolerance.