A CD1a+/CD11c+ subset of human blood dendritic cells is a direct precursor of Langerhans cells.
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-3Ralpha, 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-beta1. 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.
Ito
T
T
First Department of Internal Medicine, First Department of Pathology, Kansai Medical University, Osaka, Japan.
Inaba
M
M
Inaba
K
K
Toki
J
J
Sogo
S
S
Iguchi
T
T
Adachi
Y
Y
Yamaguchi
K
K
Amakawa
R
R
Valladeau
J
J
Saeland
S
S
Fukuhara
S
S
Ikehara
S
S
D018949:Antigens, CD1 / Q000097:blood*; D002454:Cell Differentiation / Q000276:immunology; D002469:Cell Separation; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000648:ultrastructure; D005434:Flow Cytometry; D006801:Humans; D016130:Immunophenotyping; D016167:Integrin alphaXbeta2 / Q000097:blood*; D007801:Langerhans Cells / Q000166:cytology / Q000276:immunology*; D018950:Lipopolysaccharide Receptors / Q000096:biosynthesis; D007959:Lymphocyte Culture Test, Mixed; D013234:Stem Cells / Q000166:cytology / Q000276:immunology*; D013997:Time Factors
D018949:Antigens, CD1; D016167:Integrin alphaXbeta2; D018950:Lipopolysaccharide Receptors