Sustained survivin expression from OX40 costimulatory signals drives T cell clonal expansion. Academic Article uri icon

abstract

  • Sustained signaling from the T cell receptor (TCR) and costimulatory molecules is thought necessary for generating high numbers of effector T cells. Here, we show that Survivin is controlled in peripheral T cells by OX40 cosignaling via sustained PI3k and PKB activation. Survivin is induced by OX40 independent of mitotic progression in late G1, and blocking Survivin suppresses S-phase transition and division of T cells and leads to apoptosis. Moreover, Survivin expression alone is sufficient to restore proliferation and to antagonize apoptosis in costimulation-deficient T cells and can rescue T cell expansion in vivo. Survivin allows effector T cells to accumulate in large numbers, but Bcl-2 family proteins are required for T cell survival after the phase of active division. Thus, sustained Survivin expression from costimulatory signaling maintains T cell division over time and regulates the extent of clonal expansion.

published proceedings

  • Immunity

altmetric score

  • 9

author list (cited authors)

  • Song, J., So, T., Cheng, M., Tang, X., & Croft, M.

citation count

  • 193

complete list of authors

  • Song, Jianxun||So, Takanori||Cheng, Mary||Tang, Xiaohong||Croft, Michael

publication date

  • January 1, 2005 11:11 AM