Pr. Rogers et al., OX40 promotes Bcl-xL and Bcl-2 expression and is essential for long-term survival of CD4 T cells, IMMUNITY, 15(3), 2001, pp. 445-455
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 unimpai
red in IL-2 production, cell division, and expansion. However, OX40(-/-) T
cells fall to maintain high levels of Bci-xL and Bcl-2 4-8 days after activ
ation, and undergo apoptosis. Conversely, OX40 stimulation promotes Bcl-xL
and Bcl-2 and suppresses apoptosis. Moreover, retroviral transduction of OX
40(-/-) 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 cri
tical regulator of antigen-driven T cell survival.