OX40 Promotes Bcl-xL and Bcl-2 Expression and Is Essential for Long-Term Survival of CD4 T Cells

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.