Differential Intrasplenic Migration of Dendritic Cell Subsets Tailors Adaptive Immunity

Cell Rep. 2016 Aug 30;16(9):2472-85. doi: 10.1016/j.celrep.2016.07.076. Epub 2016 Aug 18.

Abstract

Evidence suggests that distinct splenic dendritic cell (DC) subsets activate either CD4+ or CD8+ T cells in vivo. This bias has been partially ascribed to differential antigen presentation; however, all DC subsets can activate both T cell lineages in vitro. Therefore, we tested whether the organization of DC and T cell subsets in the spleen dictated this preference. We discovered that CD4+ and CD8+ T cells segregated within splenic T cell zones prior to immunization. After intravenous immunization, the two major conventional DC populations, distinguished by 33D1 and XCR1 staining, migrated into separate regions of the T cell zone: 33D1+ DCs migrated into the CD4+ T cell area, whereas XCR1+ DCs migrated into the CD8+ T cell area. Thus, the post-immunization location of each DC subset correlated with the T cell lineage it preferentially primes. Preventing this co-localization selectively impaired either CD4+ or CD8+ T cell immunity to blood-borne antigens.

Keywords: CCR7; T cell; dendritic cell; red blood cell alloimmunization; spleen.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptive Immunity*
  • Animals
  • Antigen Presentation*
  • Antigens / administration & dosage
  • Biomarkers / metabolism
  • CD4-Positive T-Lymphocytes / cytology
  • CD4-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / cytology
  • CD8-Positive T-Lymphocytes / immunology*
  • Cell Movement
  • Dendritic Cells / classification*
  • Dendritic Cells / cytology
  • Dendritic Cells / immunology
  • Erythrocyte Transfusion
  • Gene Expression
  • Immunization
  • Immunophenotyping
  • Isoantibodies / biosynthesis
  • Lipopolysaccharides / administration & dosage
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Ovalbumin / administration & dosage
  • Receptors, Chemokine / genetics
  • Receptors, Chemokine / immunology
  • Spleen / cytology
  • Spleen / immunology*

Substances

  • Antigens
  • Biomarkers
  • Isoantibodies
  • Lipopolysaccharides
  • Receptors, Chemokine
  • XC chemokine receptor 1, mouse
  • Ovalbumin