OX40 promotes Bcl-xL and Bcl-2 expression and is essential for long-term survival of CD4 T cells.
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.
Rogers
P R
PR
Division of Immunochemistry, La Jolla Institute for Allergy and Immunology, San Diego, CA 92121, USA.
Song
J
J
Gramaglia
I
I
Killeen
N
N
Croft
M
M
D000818:Animals; D017209:Apoptosis; D018106:CD28 Antigens / Q000502:physiology; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology*; D002470:Cell Survival; D002478:Cells, Cultured; D008562:Membrane Glycoproteins / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D053278:OX40 Ligand; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis*; D053262:Receptors, OX40; D018124:Receptors, Tumor Necrosis Factor; D012190:Retroviridae / Q000235:genetics; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000502:physiology*; D048069:Tumor Necrosis Factors; D051020:bcl-X Protein
C494812:Bcl2l1 protein, mouse; D018106:CD28 Antigens; D008562:Membrane Glycoproteins; D053278:OX40 Ligand; D019253:Proto-Oncogene Proteins c-bcl-2; D053262:Receptors, OX40; D018124:Receptors, Tumor Necrosis Factor; C505717:Tnfrsf4 protein, mouse; C504586:Tnfsf4 protein, mouse; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D048069:Tumor Necrosis Factors; D051020:bcl-X Protein