The TNF–TNFR family of co-signal molecules

Takanori So, Naoto Ishii

Research output: Chapter in Book/Report/Conference proceedingChapterpeer-review

79 Citations (Scopus)


Costimulatory signals initiated by the interaction between the tumor necrosis factor (TNF) ligand and cognate TNF receptor (TNFR) superfamilies promote clonal expansion, differentiation, and survival of antigen-primed CD4+ and CD8+ T cells and have a pivotal role in T-cell-mediated adaptive immunity and diseases. Accumulating evidence in recent years indicates that costimulatory signals via the subset of the TNFR superfamily molecules, OX40 (TNFRSF4), 4-1BB (TNFRSF9), CD27, DR3 (TNFRSF25), CD30 (TNFRSF8), GITR (TNFRSF18), TNFR2 (TNFRSF1B), and HVEM (TNFRSF14), which are constitutive or inducible on T cells, play important roles in protective immunity, inflammatory and autoimmune diseases, and tumor immunotherapy. In this chapter, we will summarize the findings of recent studies on these TNFR family of co-signaling molecules regarding their function at various stages of the T-cell response in the context of infection, inflammation, and cancer. We will also discuss how these TNFR co-signals are critical for immune regulation and have therapeutic potential for the treatment of T-cell-mediated diseases.

Original languageEnglish
Title of host publicationAdvances in Experimental Medicine and Biology
Number of pages32
Publication statusPublished - 2019

Publication series

NameAdvances in Experimental Medicine and Biology
ISSN (Print)0065-2598
ISSN (Electronic)2214-8019


  • 4-1BB
  • CD27
  • CD30
  • DR3
  • GITR
  • HVEM
  • OX40
  • TNFR2


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