The role of TNF superfamily members in T-cell function and diseases

Nat Rev Immunol. 2009 Apr;9(4):271-85. doi: 10.1038/nri2526.


Interactions that occur between several tumour necrosis factor (TNF)-TNF receptors that are expressed by T cells and various other immune and non-immune cell types are central to T-cell function. In this Review, I discuss the biology of four different ligand-receptor interactions - OX40 ligand and OX40, 4-1BB ligand and 4-1BB, CD70 and CD27, and TL1A and death receptor 3 - and their potential to be exploited for therapeutic benefit. Manipulating these interactions can be effective for treating diseases in which T cells have an important role, including inflammatory conditions, autoimmunity and cancer. Here, I explore how blocking or inducing the signalling pathways that are triggered by these different interactions can be an effective way to modulate immune responses.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Autoimmune Diseases* / drug therapy
  • Autoimmune Diseases* / immunology
  • Humans
  • Inflammation* / drug therapy
  • Inflammation* / immunology
  • Models, Biological
  • Neoplasms* / drug therapy
  • Neoplasms* / immunology
  • Receptors, Tumor Necrosis Factor / agonists
  • Receptors, Tumor Necrosis Factor / antagonists & inhibitors
  • Receptors, Tumor Necrosis Factor / physiology
  • Signal Transduction / drug effects
  • Signal Transduction / physiology
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / physiology*
  • Tumor Necrosis Factor Inhibitors
  • Tumor Necrosis Factors / agonists
  • Tumor Necrosis Factors / physiology*


  • Receptors, Tumor Necrosis Factor
  • Tumor Necrosis Factor Inhibitors
  • Tumor Necrosis Factors