TY - JOUR
T1 - OX40 promotes Bcl-xL and Bcl-2 expression and is essential for long-term survival of CD4 T cells
AU - Rogers, Paul R.
AU - Song, Jianxun
AU - Gramaglia, Irene
AU - Killeen, Nigel
AU - Croft, Michael
N1 - Funding Information:
This work was funded by NIH grant AI42944 to Michael Croft. This is manuscript #395 from the La Jolla Institute for Allergy and Immunology. The authors would like to thank Dr. Abul Abbas for the generous gift of the MSCV vector containing Bcl-xL, and acknowledge Dr. Bill Sha from whom the MSCV vector originated. The authors would also like to thank Dr. Doug Green for providing cDNA for Bcl-2 and Dr. Jianyong Huang for assistance with Western blotting and retroviral transduction.
PY - 2001
Y1 - 2001
N2 - 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.
AB - 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.
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U2 - 10.1016/S1074-7613(01)00191-1
DO - 10.1016/S1074-7613(01)00191-1
M3 - Article
C2 - 11567634
AN - SCOPUS:0034812971
SN - 1074-7613
VL - 15
SP - 445
EP - 455
JO - Immunity
JF - Immunity
IS - 3
ER -