The costimulation-regulated duration of PKB activation controls T cell longevity

Nat Immunol. 2004 Feb;5(2):150-8. doi: 10.1038/ni1030. Epub 2004 Jan 18.

Abstract

A brief antigenic stimulus can promote T cell proliferation, but the duration and nature of intracellular signals required for survival are unclear. Here we show that in the absence of OX40 costimulation, antigen-activated CD4+ cells are short-lived because the activity of protein kinase B (PKB; also known as Akt) is not maintained over time. Activated T cells that express a dominant-negative variant of PKB also undergo apoptosis, reproducing the OX40-deficient phenotype. In contrast, an active form of PKB prevents downregulation of antiapoptotic proteins in OX40-deficient T cells, rescues antigen-induced cell survival in vivo, and controls inflammation in recall responses. Thus, sustained and periodic PKB signaling has an integral role in regulating T cell longevity.

Publication types

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

MeSH terms

  • Animals
  • Apoptosis
  • Cell Division
  • Cell Survival
  • Inflammation / enzymology
  • Inflammation / immunology
  • Mice
  • Mice, Knockout
  • Mice, Transgenic
  • Protein-Serine-Threonine Kinases*
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / metabolism*
  • Proto-Oncogene Proteins c-akt
  • Receptors, Antigen, T-Cell / genetics
  • Receptors, OX40
  • Receptors, Tumor Necrosis Factor / deficiency
  • Receptors, Tumor Necrosis Factor / genetics
  • Signal Transduction
  • T-Lymphocytes / cytology
  • T-Lymphocytes / enzymology*
  • T-Lymphocytes / immunology*

Substances

  • Proto-Oncogene Proteins
  • Receptors, Antigen, T-Cell
  • Receptors, OX40
  • Receptors, Tumor Necrosis Factor
  • Tnfrsf4 protein, mouse
  • Protein-Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-akt