CD1a expression defines an interleukin-12 producing population of human dendritic cells

摘要

Human and murine dendritic cell (DC) subsets are often defined by phenotypic features that predict their functional characteristics. In humans and mice, DC have been shown to have the ability to polarize naive CD4 T cells to a T helper type 1 (Th1) or Th2 phenotype. However, human myeloid DC generated from monocytes (monocyte-derived DC) have often been regarded as a homogeneous population, both phenotypically and functionally. Monocytes give rise to subpopulations of DC in vitro that can be separated on the basis of their expression of CD1a, a well-described DC subset marker. Importantly, we show that the CD1a⁺ DC subset produces significant quantities of interleukin-12p70 (IL-12p70) upon stimulation and, similar to the murine CD8α⁺ DC subset, can polarize naive CD4⁺ T cells to a Th1 phenotype. In contrast, CD1a⁻ DC, similar to murine CD8α⁻ DC, do not produce significant amounts of IL-12p70 upon stimulation or polarize T cells to a Th1 phenotype. Like monocyte-derived DC, CD1a⁺ and CD1a⁻ DC subsets obtained from CD34⁺ haematopoietic progenitors under distinct culture conditions were found to have these same features, suggesting that CD1a expression is a marker for myeloid DC that are a major source of IL-12 and Th1 CD4⁺ T cell polarization in man.