OX40 promotes Bcl-xL and Bcl-2 expression and is essential for long-term survival of CD4 T cells.
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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.
author list (cited authors)
Rogers, P. R., Song, J., Gramaglia, I., Killeen, N., & Croft, M.
complete list of authors
Rogers, PR||Song, J||Gramaglia, I||Killeen, N||Croft, M