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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.