OX40 promotes Bcl-xL and Bcl-2 expression and is essential for long-term survival of CD4 T cells

Immunity. 2001 Sep;15(3):445-55. doi: 10.1016/s1074-7613(01)00191-1.

Abstract

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Apoptosis
  • CD28 Antigens / physiology
  • CD4-Positive T-Lymphocytes / physiology*
  • Cell Survival
  • Cells, Cultured
  • Membrane Glycoproteins / physiology
  • Mice
  • Mice, Transgenic
  • 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
  • bcl-X Protein

Substances

  • Bcl2l1 protein, mouse
  • CD28 Antigens
  • Membrane Glycoproteins
  • Proto-Oncogene Proteins c-bcl-2
  • Receptors, OX40
  • Receptors, Tumor Necrosis Factor
  • Tnfrsf4 protein, mouse
  • Tnfsf4 protein, mouse
  • Tumor Necrosis Factor Receptor Superfamily, Member 7
  • Tumor Necrosis Factors
  • bcl-X Protein