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*
First Department of Internal Medicine and
First Department of Pathology, Kansai Medical University, Moriguchi, Osaka, Japan;
Department of Zoology, Kyoto University, Sakyo, Kyoto, Japan;
Cellular Technology Institute, Otsuka Pharmaceutical Co., Tokushima, Japan; and
¶
Schering-Plough, Laboratory for Immunological Research, Dardilly, France
Based on the relative expression of CD11c and CD1a, we have
identified three fractions of dendritic cells (DCs) in human peripheral
blood, including a direct precursor of Langerhans cells (LCs). The
first two fractions were CD11c+ DCs, comprised of a major
CD1a+/CD11c+ population (fraction 1), and a
minor CD1a-/CD11c+ component (fraction 2).
Both CD11c+ fractions displayed a monocyte-like morphology,
endocytosed FITC-dextran, expressed CD45RO and myeloid markers such as
CD13 and CD33, and possessed the receptor for GM-CSF. The third
fraction was comprised of CD1a-/CD11c- DCs
(fraction 3) and resembled plasmacytoid T cells. These did not uptake
FITC-dextran, were negative for myeloid markers (CD13/CD33), and
expressed CD45RA and a high level of IL-3R
, but not GM-CSF
receptors. After culture with IL-3, fraction 3 acquired the
characteristics of mature DCs; however, the expression of CD62L (lymph
node-homing molecules) remained unchanged, indicating that fraction 3
can be a precursor pool for previously described plasmacytoid T cells
in lymphoid organs. Strikingly, the
CD1a+/CD11c+ DCs (fraction 1) quickly acquired
LC characteristics when cultured in the presence of GM-CSF + IL-4 +
TGF-
1. Thus, E-cadherin, Langerin, and Lag Ag were expressed within
1 day of culture, and typical Birbeck granules were observed. In
contrast, neither CD1a-/CD11c+ (fraction 2)
nor CD1a-/CD11c- (fraction 3) cells had the
capacity to differentiate into LCs. Furthermore, CD14+
monocytes only expressed E-cadherin, but lacked the other LC markers
after culture in these cytokines. Therefore,
CD1a+/CD11c+ DCs are the direct precursors of
LCs in peripheral blood.
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