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 acid myeloid markers such as CD13 and CD33, and possessed the receptor for GR I-CSP. 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 alpha, 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-beta 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.