The capacity of the TNF family members 4-1BBL, OX40L, CD70, GITRL, CD30L and LIGHT to costimulate human T cells

Eur J Immunol. 2008 Oct;38(10):2678-88. doi: 10.1002/eji.200838250.


Activating signals generated by members of the tumour necrosis factor receptor superfamily upon interaction with their cognate ligands play important roles in T-cell responses. Members of the tumour necrosis factor family namely 4-1BBL, OX40L, CD70, GITRL, LIGHT and CD30L have been described to function as costimulatory molecules by binding such receptors on T cells. Using our recently described system of T-cell stimulator cells we have performed the first study where all these molecules have been assessed and compared regarding their capacity to costimulate proliferation and cytokine production of human T cells. 4-1BBL, which we found to be the most potent molecule in this group, was able to mediate sustained activation and proliferation of human T cells. OX40L and CD70 were also strong inducers of T-cell proliferation, whereas the costimulatory capacity of human GITRL was significantly lower. Importantly CD30L and LIGHT consistently failed to act costimulatory on human T cells, and we therefore suggest that these molecules might be functionally distinct from the costimulatory members of this family.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 4-1BB Ligand / immunology
  • 4-1BB Ligand / metabolism
  • CD27 Ligand / immunology
  • CD27 Ligand / metabolism
  • CD30 Ligand / immunology
  • CD30 Ligand / metabolism
  • Cell Proliferation
  • Humans
  • Lymphocyte Activation*
  • OX40 Ligand / immunology
  • OX40 Ligand / metabolism
  • Receptors, Tumor Necrosis Factor / metabolism
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism
  • Tumor Necrosis Factor Ligand Superfamily Member 14 / immunology
  • Tumor Necrosis Factor Ligand Superfamily Member 14 / metabolism
  • Tumor Necrosis Factors / immunology*
  • Tumor Necrosis Factors / metabolism


  • 4-1BB Ligand
  • CD27 Ligand
  • CD30 Ligand
  • CD70 protein, human
  • OX40 Ligand
  • Receptors, Tumor Necrosis Factor
  • TNFSF14 protein, human
  • TNFSF18 protein, human
  • TNFSF4 protein, human
  • TNFSF8 protein, human
  • Tumor Necrosis Factor Ligand Superfamily Member 14
  • Tumor Necrosis Factors