Cross-linking of 4-1BB up-regulates IL-13 expression in CD8(+) T lymphocytes

Cytokine. 2006 Jan 21;33(2):87-94. doi: 10.1016/j.cyto.2005.12.003. Epub 2006 Feb 20.


4-1BB, one of co-stimulatory molecules, is a member of TNF receptor superfamily and expressed on T cells upon TCR ligation. We have shown that 4-1BB is a co-stimulatory molecule enhancing cell cycle progression and inhibiting activation-induced cell death of CD8+ T cells by enhancing TCR signaling pathways. Here, we first report that the cross-linking of 4-1BB increased the expression of IL-13 mRNA and protein, and its secretion apparently via calcineurin, a Ca2+/calmodulin-dependent phosphatase. Ligation of 4-1BB with p815-m-4-1BBL evoked intracellular Ca2+ level in CD8+ T cells. CD8+ T cells express IL-13 receptor alpha1 mRNA. Incubation with anti-IL-13 blocking mAb reduced proliferation of CD8+ T cells enhanced by 4-1BB, and the treatment of CD3/4-1BB-ligated CD8+ T cells with recombinant IL-13 enhances cell proliferation, indicating that 4-1BB-induced IL-13 expression is partially responsible for the CD8+ T cell expansion in an autocrine or paracrine manner.

MeSH terms

  • 4-1BB Ligand / metabolism*
  • Animals
  • CD8-Positive T-Lymphocytes / metabolism*
  • Calcium / metabolism
  • Cross-Linking Reagents / metabolism*
  • Cytosol / metabolism
  • Interleukin-13 / metabolism*
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Up-Regulation*


  • 4-1BB Ligand
  • Cross-Linking Reagents
  • Interleukin-13
  • Calcium