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Flt3 ligand expands dendritic cell numbers in normal and malignant murine prostate
Author(s) -
Moghaddami Mahin,
Swart Bernadette,
Reynolds Pakathip,
Diener Kerrilyn,
Brown Michael P
Publication year - 2002
Publication title -
immunology and cell biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.999
H-Index - 104
eISSN - 1440-1711
pISSN - 0818-9641
DOI - 10.1046/j.1440-1711.2002.01100.x
Subject(s) - mhc class ii , dendritic cell , cd11c , prostate , biology , cd40 , cd86 , cancer research , cd80 , major histocompatibility complex , immune system , immunology , t cell , cytotoxic t cell , cancer , in vitro , biochemistry , genetics , phenotype , gene
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 + , CD8α − ). 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.