Expression and Function of 4-1BB and 4-1BB Ligand on Murine Dendritic Cells

Int Immunol. 2002 Mar;14(3):275-86. doi: 10.1093/intimm/14.3.275.

Abstract

4-1BB (CDw137) and its ligand (4-1BBL) have been implicated in cellular immune responses. To further characterize the expression and function of 4-1BBL, we newly generated an anti-mouse 4-1BBL mAb (TKS-1), which can inhibit the interaction of 4-1BBL with 4-1BB. Flow cytometric analyses using TKS-1 and an anti-mouse 4-1BB mAb indicated that 4-1BB was inducible on both CD4(+) and CD8(+) splenic T cells by stimulation with immobilized anti-CD3 mAb, but 4-1BBL was not expressed on resting or activated T cells. 4-1BBL expression was inducible on splenic B cells by stimulation with anti-IgM antibody plus anti-CD40 mAb, on peritoneal macrophages by stimulation with lipopolysaccharide (LPS) and on splenic dendritic cells (DC) by stimulation with anti-CD40 mAb or LPS. Interestingly, splenic DC expressed 4-1BB constitutively, which was down-regulated by anti-CD40 stimulation. Co-culture of splenic DC with 4-1BBL-transfected cells or 4-1BBL-expressing tumor cell lines led to cytokine (IL-6 and IL-12) production and co-stimulatory molecule up-regulation by splenic DC, indicating that 4-1BBL can directly activate DC. Moreover, IL-12 production by anti-CD40-stimulated DC was partially inhibited by TKS-1. These results suggest that 4-1BB expressed on DC may be involved in DC activation through DC--tumor interaction and DC--DC interaction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 4-1BB Ligand
  • Animals
  • Antibodies, Monoclonal / immunology
  • Antigens, CD
  • B-Lymphocytes / immunology
  • CD40 Antigens / metabolism
  • Cells, Cultured
  • Dendritic Cells / immunology*
  • Female
  • Interleukin-12 / biosynthesis
  • Macrophages / immunology
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Inbred DBA
  • Mice, Inbred Strains
  • Mice, Transgenic
  • Receptors, Nerve Growth Factor / genetics
  • Receptors, Nerve Growth Factor / metabolism*
  • Receptors, Nerve Growth Factor / physiology*
  • Receptors, Tumor Necrosis Factor / genetics
  • Receptors, Tumor Necrosis Factor / metabolism*
  • Receptors, Tumor Necrosis Factor / physiology*
  • T-Lymphocytes / immunology
  • Tumor Necrosis Factor Receptor Superfamily, Member 9
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / metabolism*
  • Tumor Necrosis Factor-alpha / physiology*

Substances

  • 4-1BB Ligand
  • Antibodies, Monoclonal
  • Antigens, CD
  • CD40 Antigens
  • Receptors, Nerve Growth Factor
  • Receptors, Tumor Necrosis Factor
  • Tnfrsf9 protein, mouse
  • Tnfsf9 protein, mouse
  • Tumor Necrosis Factor Receptor Superfamily, Member 9
  • Tumor Necrosis Factor-alpha
  • Interleukin-12