Helminth-conditioned dendritic cells prime CD4+ T cells to IL-4 production in vivo

J Immunol. 2014 Sep 15;193(6):2709-17. doi: 10.4049/jimmunol.1400374. Epub 2014 Aug 8.

Abstract

Dendritic cells (DC) are critical for the initiation of immune responses; however, their role in priming IL-4-producing Th2 cells in vivo is not fully understood. We used a model of intradermal injection with fluorescent-labeled, nonviable larvae from the helminth parasite nonviable Nippostrongylus brasiliensis L3 larvae (Nb), a strong inducer of Th2 responses, together with IL-4-GFP reporter mice that enable a sensitive detection of IL-4 production to examine the contribution of DC to the priming of IL-4-producing CD4(+) T cells in vivo. We found that parasite material is taken up by two distinct DC populations in draining lymph nodes: a mostly CD11c(int)MHC class II (MHCII)(hi)CD11b(+)Ly6C(-) dermal DC population and a CD11c(hi)MHCII(int)CD11b(+)Ly6C(+) monocyte-derived DC population. After Nb treatment, these two DC populations appeared in the draining lymph nodes in comparable numbers and with similar kinetics; however, treatment with pertussis toxin blocked the migration of dermal DC and the priming of IL-4-producing T cells, but only partially affected monocyte-derived DC numbers. In line with this observation, transfer of OVA-loaded CD11c(int)MHCII(hi) DC from Nb-treated mice into naive hosts could sensitize OVA-specific CD4(+) T cells to IL-4 production, whereas transfer of CD11c(int)MHCII(hi) DC from naive mice, or CD11c(hi)MHCII(int) DC from Nb-treated or naive mice, induced CD4(+) T cell expansion but no IL-4 production. Phenotypic analysis of Nb-loaded CD11c(int)MHCII(hi) DC revealed expression of programmed death ligand 2, CD301b, IFN regulatory factor 4, and moderate upregulation of OX40 ligand. However, thymic stromal lymphopoietin and OX40 ligand were not required for Th2 priming. Thus, our data suggest that appropriate stimuli can induce DC to express the unique signals sufficient to direct CD4(+) T cells to Th2 differentiation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Ly / biosynthesis
  • CD11c Antigen / biosynthesis
  • Cell Differentiation / immunology
  • Cytokines / genetics
  • Cytokines / immunology
  • Dendritic Cells / immunology*
  • Green Fluorescent Proteins
  • Histocompatibility Antigens Class II / biosynthesis
  • Histocompatibility Antigens Class II / immunology
  • Interferon Regulatory Factors / biosynthesis
  • Interleukin-33
  • Interleukin-4 / biosynthesis*
  • Interleukin-4 / immunology
  • Interleukins / immunology
  • Larva / immunology
  • Lectins, C-Type / biosynthesis
  • Lymph Nodes / immunology
  • Lymphocyte Activation / immunology
  • Membrane Glycoproteins / biosynthesis
  • Membrane Glycoproteins / immunology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Nippostrongylus / immunology*
  • OX40 Ligand
  • Programmed Cell Death 1 Ligand 2 Protein / biosynthesis
  • Th2 Cells / immunology*
  • Tumor Necrosis Factors / biosynthesis
  • Tumor Necrosis Factors / immunology

Substances

  • Antigens, Ly
  • CD11c Antigen
  • Cytokines
  • Histocompatibility Antigens Class II
  • Il33 protein, mouse
  • Interferon Regulatory Factors
  • Interleukin-33
  • Interleukins
  • Lectins, C-Type
  • Ly-6C antigen, mouse
  • MGL2 protein, mouse
  • Membrane Glycoproteins
  • OX40 Ligand
  • Pdcd1lg2 protein, mouse
  • Programmed Cell Death 1 Ligand 2 Protein
  • Tnfsf4 protein, mouse
  • Tumor Necrosis Factors
  • interferon regulatory factor-4
  • Green Fluorescent Proteins
  • Interleukin-4
  • thymic stromal lymphopoietin