Batf3-independent langerin- CX3CR1- CD8α+ splenic DCs represent a precursor for classical cross-presenting CD8α+ DCs

J Leukoc Biol. 2014 Dec;96(6):1001-10. doi: 10.1189/jlb.1A0314-130R. Epub 2014 Aug 28.


This study tests the hypothesis that CD8α(+) DCs in the spleen of mice contain an immature precursor for functionally mature, "classical" cross-presenting CD8α(+) DCs. The lymphoid tissues contain a network of phenotypically distinct DCs with unique roles in surveillance and immunity. Splenic CD8α(+) DCs have been shown to exhibit a heightened capacity for phagocytosis of cellular material, secretion of IL-12, and cross-priming of CD8(+) T cells. However, this population can be subdivided further on the basis of expression of both langerin/CD207 and CX(3)CR1. We therefore evaluated the functional capacities of these different subsets. The CX(3)CR1(+) CD8α(+) DC subset does not express langerin and does not exhibit the classical features above. The CX(3)CR1(-) CD8α(+) DC can be divided into langerin-positive and negative populations, both of which express DEC205, Clec9A, and high basal levels of CD86. However, the langerin(+) CX(3)CR1(-) CD8α(+) subset has a superior capacity for acquiring cellular material and producing IL-12 and is more susceptible to activation-induced cell death. Significantly, following purification and adoptive transfer into new hosts, the langerin(-) CX(3)CR1(-) CD8α(+) subset survives longer, up-regulates expression of langerin, and becomes more susceptible to activation-induced cell death. Last, in contrast to langerin(+) CX(3)CR1(-) CD8α(+), the langerin(-) CX(3)CR1(-) CD8α(+) are still present in Batf3(-/-) mice. We conclude that the classical attributes of CD8α(+) DC are confined primarily to the langerin(+) CX(3)CR1(-) CD8α(+) DC population and that the langerin(-) CX(3)CR1(-) subset represents a Batf3-independent precursor to this mature population.

Keywords: dendritic cell differentiation; differentiation of antigen presenting cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptive Immunity*
  • Adoptive Transfer
  • Animals
  • Antigen Presentation
  • Antigens, Differentiation / analysis*
  • Antigens, Surface / analysis
  • Antigens, Surface / biosynthesis
  • Antigens, Surface / genetics
  • Basic-Leucine Zipper Transcription Factors / analysis
  • CD8 Antigens / analysis
  • CD8-Positive T-Lymphocytes / immunology
  • CX3C Chemokine Receptor 1
  • Cell Differentiation
  • Cell Lineage
  • Cells, Cultured
  • Cellular Senescence
  • Crosses, Genetic
  • Dendritic Cells / chemistry
  • Dendritic Cells / classification*
  • Dendritic Cells / immunology
  • Female
  • Galactosylceramides / immunology
  • Histocompatibility Antigens Class I / immunology
  • Immune Tolerance / immunology
  • Immunophenotyping
  • Interleukin-12 Subunit p40 / biosynthesis
  • Lectins, C-Type / analysis
  • Lectins, C-Type / biosynthesis
  • Lectins, C-Type / genetics
  • Male
  • Mannose-Binding Lectins / analysis
  • Mannose-Binding Lectins / biosynthesis
  • Mannose-Binding Lectins / genetics
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Phagocytosis / immunology
  • Receptors, Chemokine / analysis
  • Repressor Proteins / analysis
  • Spleen / cytology
  • Spleen / immunology


  • Antigens, Differentiation
  • Antigens, Surface
  • Basic-Leucine Zipper Transcription Factors
  • CD8 Antigens
  • CD8 antigen, alpha chain
  • CX3C Chemokine Receptor 1
  • Cd207 protein, mouse
  • Cx3cr1 protein, mouse
  • Galactosylceramides
  • Histocompatibility Antigens Class I
  • Interleukin-12 Subunit p40
  • Lectins, C-Type
  • Mannose-Binding Lectins
  • Receptors, Chemokine
  • Repressor Proteins
  • SNFT protein, mouse
  • alpha-galactosylceramide