Intracellular signals of T cell costimulation

Cell Mol Immunol. 2008 Aug;5(4):239-47. doi: 10.1038/cmi.2008.30.

Abstract

Ligation of T cell receptor (TCR) alone is insufficient to induce full activation of T lymphocytes. Additional ligand-receptor interactions (costimulation) on antigen presenting cells (APCs) and T cells are required. T cell costimulation has been shown to be essential for eliciting efficient T cell responses, involving all phases during T cell development. However, the mechanisms by which costimulation affects the function of T cells still need to be elucidated. In recent years, advances have been made in studies of costimulation as potential therapies in cancer, infectious disease as well as autoimmune disease. In this review, we discussed intracellular costimulation signals that regulate T cell proliferation, cell cycle progression, cytokine production, survival, and memory development. In general, the pathway of phosphoinositide-3 kinase (PI3K)/protein kinase B (PKB, also known as Akt)/nuclear factor kappaB (NF-kappaB) might be central to many costimulatory effects. Through these pathways, costimulation controls T-cell expansion and proliferation by maintenance of survivin and aurora B expression, and sustains long-term T-cell survival and memory development by regulating the expression of bcl-2 family members.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antigen-Presenting Cells / immunology
  • Antigen-Presenting Cells / metabolism*
  • Aurora Kinase B
  • Aurora Kinases
  • Cell Proliferation
  • Cytokines / immunology
  • Cytokines / metabolism
  • Humans
  • Immunologic Memory
  • Lymphocyte Activation
  • Microtubule-Associated Proteins / metabolism
  • NF-kappa B / metabolism
  • Phosphatidylinositol 3-Kinases / metabolism
  • Protein-Serine-Threonine Kinases / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Receptors, Antigen, T-Cell / immunology
  • Receptors, Antigen, T-Cell / metabolism*
  • Signal Transduction*
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism*

Substances

  • Cytokines
  • Microtubule-Associated Proteins
  • NF-kappa B
  • Proto-Oncogene Proteins c-bcl-2
  • Receptors, Antigen, T-Cell
  • Phosphatidylinositol 3-Kinases
  • AURKB protein, human
  • Aurora Kinase B
  • Aurora Kinases
  • Protein-Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-akt