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Blood, 15 April 2002, Vol. 99, No. 8, pp. 2752-2759
HEMATOPOIESIS
Intrathymic and extrathymic development of human plasmacytoid
dendritic cell precursors in vivo
Kees Weijer,
Christel H. Uittenbogaart,
Arie Voordouw,
Franka Couwenberg,
Jurgen Seppen,
Bianca Blom,
Florry A. Vyth-Dreese, and
Hergen Spits
From the Division of Immunology, Netherlands Cancer
Institute, Amsterdam, The Netherlands.
The development of plasmacytoid dendritic cells (pDC2) from human
CD34+ stem cells in vivo was studied in
RAG-2 / interleukin (IL)-2R / mice
that lack functional T and B cells and natural killer cells. CD34+ cells isolated from fetal liver or thymus were
labeled with 5- and 6-carboxyfluorescein diacetate succinimidyl ester
(CFSE) and were injected into a human thymus grafted subcutaneously in
the RAG-2/ IL-2R/ mice. One to 4 weeks later the CFSE label was found not only in T cells but also in
CD123+/high CD4+CD45RA+ pDC2,
indicating that the CD34+ cells can develop into pDC2
within a thymus. In addition to pDC2, CFSE-labeled dendritic cells with
a mature phenotype, determined by the cell surface markers CD11c, CD83,
and CD80, were found in the injected human thymus graft. pDC2 was not
found in the periphery of mice carrying a human thymic graft,
indicating that the intrathymic pDC2 failed to emigrate from the
thymus. We also demonstrate that pDC2 can develop outside the thymus
because relatively high percentages of pDC2 were found in the periphery
after the intravenous injection of CD34+CD38
fetal liver cells in RAG-2/ IL-2R/
mice without a human thymus graft. These data indicate that the thymus
and the peripheral pDC2 develop independently of each other.
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