OX40 Promotes Bcl-xL and Bcl-2 Expression and Is Essential for Long-Term Survival of CD4 T Cells

• Published in: Immunity (Cambridge, Mass.) Mass.), 2001-09, Vol.15 (3), p.445-455
• Main Authors: Rogers, Paul R, Song, Jianxun, Gramaglia, Irene, Killeen, Nigel, Croft, Michael
• Format: Article
• Language: English
• Subjects: Animals; Apoptosis; Bcl-2 protein; bcl-X Protein; Bcl-xL protein; CD28 Antigens - physiology; CD4 antigen; CD4-Positive T-Lymphocytes - physiology; Cell Survival; Cells, Cultured; Membrane Glycoproteins - physiology; Mice; Mice, Transgenic; OX40 antigen; Proto-Oncogene Proteins c-bcl-2 - analysis; Receptors, OX40; Receptors, Tumor Necrosis Factor; Retroviridae - genetics; Tumor Necrosis Factor Receptor Superfamily, Member 7 - physiology; Tumor Necrosis Factors
• ISSN: 1074-7613; 1097-4180
• DOI: 10.1016/S1074-7613(01)00191-1

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.