OX40 promotes Bcl-xL and Bcl-2 expression and is essential for long-term survival of CD4 T cells

Paul R. Rogers, Jianxun Song, Irene Gramaglia, Nigel Killeen, Michael Croft

Research output: Contribution to journalArticle

478 Scopus citations

Abstract

It is important to understand which molecules are essential for long-lived immunity. We show that OX40 (CD134) is required with CD28 for the survival of CD4 T cells following antigen-driven expansion. In contrast to CD28-/- T cells, which show defects early, OX40-/- T cells are relatively unimpaired in IL-2 production, cell division, and expansion. However, OX40-/- T cells fail to maintain high levels of Bcl-xL and Bcl-2 4-8 days after activation, and undergo apoptosis. Conversely, OX40 stimulation promotes Bcl-xL and Bcl-2 and suppresses apoptosis. Moreover, retroviral transduction of OX40-/- T cells with Bcl-xL or Bcl-2 reverses their survival defect. Thus, a temporal relationship exists between CD28 and OX40, with OX40 being a critical regulator of antigen-driven T cell survival.

Original languageEnglish (US)
Pages (from-to)445-455
Number of pages11
JournalImmunity
Volume15
Issue number3
DOIs
StatePublished - Jan 1 2001

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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