Sustained survivin expression from OX40 costimulatory signals drives T cell clonal expansion

Jianxun Song, Takanori So, Mary Cheng, Xiaohong Tang, Michael Croft

Research output: Contribution to journalArticle

166 Scopus citations

Abstract

Sustained signaling from the T cell receptor (TCR) and costimulatory molecules is thought necessary for generating high numbers of effector T cells. Here, we show that Survivin is controlled in peripheral T cells by OX40 cosignaling via sustained PI3k and PKB activation. Survivin is induced by OX40 independent of mitotic progression in late G1, and blocking Survivin suppresses S-phase transition and division of T cells and leads to apoptosis. Moreover, Survivin expression alone is sufficient to restore proliferation and to antagonize apoptosis in costimulation-deficient T cells and can rescue T cell expansion in vivo. Survivin allows effector T cells to accumulate in large numbers, but Bcl-2 family proteins are required for T cell survival after the phase of active division. Thus, sustained Survivin expression from costimulatory signaling maintains T cell division over time and regulates the extent of clonal expansion.

Original languageEnglish (US)
Pages (from-to)621-631
Number of pages11
JournalImmunity
Volume22
Issue number5
DOIs
StatePublished - May 1 2005

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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