Efficient presentation of soluble antigen by cultured human dendritic cells is maintained by granulocyte/macrophage colony-stimulating factor plus interleukin 4 and downregulated by tumor necrosis factor α

Federica Sallusto, Antonio Lanzavecchia

Research output: Contribution to journalArticle

Abstract

Using granulocyte/macrophage colony-stimulating factor (GM-CSF) and interleukin 4 we have established dendritic cell (DC) lines from blood mononuclear cells that maintain the antigen capturing and processing capacity characteristic of immature dendritic cells in vivo. These cells have typical dendritic morphology, express high levels of major histocompatibility complex (MHC) class I and class II molecules, CD1, FC7RII, CD40, B7, CD44, and ICAM-1, and lack CD14. Cultured DCs are highly stimulatory in mixed leukocyte reaction (MLR) and are also capable of triggering cord blood naive T cells. Most strikingly, these DCs are as efficient as antigen-specific B cells in presenting tetanus toxoid (TT) to specific T cell clones. Their efficiency of antigen presentation can be further enhanced by specific antibodies via FcR-mediated antigen uptake. Incubation of these cultured DCs with tumor necrosis factor α (TNF-α) or soluble CD40 ligand (CD40L) for 24 h results in an increased surface expression of MHC class I and class II molecules, B7, and ICAM-1 and in the appearance of the CD44 exon 9 splice variant (CD44-v9); by contrast, FcγRII is markedly and sometimes completely downregulated. The functional consequences of the short contact with TNF-α are an increased T cell stimulatory capacity in MLR, but a 10-fold decrease in presentation of soluble TT and a 100-fold decrease in presentation of TT-immunoglobulin G complexes.

Original languageEnglish
Pages (from-to)887-896
Number of pages10
JournalJournal of Immunology
Volume200
Issue number3
DOIs
Publication statusPublished - Feb 1 2018
Externally publishedYes

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Tetanus Toxoid
Antigen Presentation
Granulocyte-Macrophage Colony-Stimulating Factor
Interleukin-4
Dendritic Cells
Mixed Lymphocyte Culture Test
Down-Regulation
Tumor Necrosis Factor-alpha
Intercellular Adhesion Molecule-1
Major Histocompatibility Complex
T-Lymphocytes
B7 Antigens
Antigens
CD40 Ligand
Fetal Blood
Exons
Blood Cells
B-Lymphocytes
Clone Cells
Immunoglobulin G

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

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abstract = "Using granulocyte/macrophage colony-stimulating factor (GM-CSF) and interleukin 4 we have established dendritic cell (DC) lines from blood mononuclear cells that maintain the antigen capturing and processing capacity characteristic of immature dendritic cells in vivo. These cells have typical dendritic morphology, express high levels of major histocompatibility complex (MHC) class I and class II molecules, CD1, FC7RII, CD40, B7, CD44, and ICAM-1, and lack CD14. Cultured DCs are highly stimulatory in mixed leukocyte reaction (MLR) and are also capable of triggering cord blood naive T cells. Most strikingly, these DCs are as efficient as antigen-specific B cells in presenting tetanus toxoid (TT) to specific T cell clones. Their efficiency of antigen presentation can be further enhanced by specific antibodies via FcR-mediated antigen uptake. Incubation of these cultured DCs with tumor necrosis factor α (TNF-α) or soluble CD40 ligand (CD40L) for 24 h results in an increased surface expression of MHC class I and class II molecules, B7, and ICAM-1 and in the appearance of the CD44 exon 9 splice variant (CD44-v9); by contrast, FcγRII is markedly and sometimes completely downregulated. The functional consequences of the short contact with TNF-α are an increased T cell stimulatory capacity in MLR, but a 10-fold decrease in presentation of soluble TT and a 100-fold decrease in presentation of TT-immunoglobulin G complexes.",
author = "Federica Sallusto and Antonio Lanzavecchia",
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