The role of OX40-mediated co-stimulation in T-cell activation and survival

Crit Rev Immunol. 2009;29(3):187-201. doi: 10.1615/critrevimmunol.v29.i3.10.


The extent of T-cell activation, proliferation, and survival that follows T-cell receptor (TCR) ligation is controlled by several factors, including the strength of TCR stimulation, the availability of prosurvival cytokines, and the presence or absence of co-stimulatory signals. In addition to engagement of the CD28 co-stimulatory receptor by its natural ligands, B7.1 (CD80) and B7.2 (CD86), recent work has begun to elucidate the mechanisms by which signaling through the OX40 (CD134) co-stimulatory receptor, a member of the tumor necrosis factor receptor (TNFR) superfamily, affects T-cell responses. Importantly, OX40 ligation has been shown to augment CD4 and CD8 T-cell clonal expansion, effector differentiation, survival, and in some cases, abrogate the suppressive activity of regulatory FoxP3+CD25+CD4+ T cells. In this review, we focus on the mechanisms regulating OX40 expression on activated T cells as well as the role of OX40-mediated co-stimulation in boosting T-cell clonal expansion, effector differentiation, and survival.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antigens, CD
  • Cell Differentiation
  • Cell Proliferation
  • Cell Survival / immunology*
  • Forkhead Transcription Factors
  • Gene Expression Regulation / immunology
  • Humans
  • Lymphocyte Activation / immunology*
  • OX40 Ligand / genetics
  • OX40 Ligand / immunology
  • OX40 Ligand / metabolism
  • Receptors, Antigen, T-Cell / immunology
  • Receptors, Antigen, T-Cell / metabolism
  • Receptors, OX40 / genetics
  • Receptors, OX40 / immunology
  • Receptors, OX40 / metabolism*
  • Signal Transduction / immunology
  • T-Lymphocyte Subsets / cytology
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / metabolism*
  • T-Lymphocytes, Regulatory / cytology
  • T-Lymphocytes, Regulatory / immunology
  • T-Lymphocytes, Regulatory / metabolism*


  • Antigens, CD
  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • OX40 Ligand
  • Receptors, Antigen, T-Cell
  • Receptors, OX40