A CD1a+/CD11c+ subset of human blood dendritic cells is a direct precursor of Langerhans cells

J Immunol. 1999 Aug 1;163(3):1409-19.

Abstract

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, CD1 / blood*
  • Cell Differentiation / immunology
  • Cell Separation
  • Cells, Cultured
  • Dendritic Cells / cytology
  • Dendritic Cells / immunology*
  • Dendritic Cells / ultrastructure
  • Flow Cytometry
  • Humans
  • Immunophenotyping
  • Integrin alphaXbeta2 / blood*
  • Langerhans Cells / cytology
  • Langerhans Cells / immunology*
  • Lipopolysaccharide Receptors / biosynthesis
  • Lymphocyte Culture Test, Mixed
  • Stem Cells / cytology
  • Stem Cells / immunology*
  • Time Factors

Substances

  • Antigens, CD1
  • Integrin alphaXbeta2
  • Lipopolysaccharide Receptors