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

Jianxun Song, Shahram Salek-Ardakani, Paul R. Rogers, Mary Cheng, Luk Van Parijs, Michael Croft

Research output: Contribution to journalArticlepeer-review

151 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)150-158
Number of pages9
JournalNature Immunology
Volume5
Issue number2
DOIs
StatePublished - Feb 2004

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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