CD28 Costimulation Can Promote T Cell Survival by Enhancing the Expression of Bcl-XL

Immunity. 1995 Jul;3(1):87-98. doi: 10.1016/1074-7613(95)90161-2.

Abstract

T cell activation through the TCR can result in either cell proliferation or cell death. The role of costimulatory receptors in regulating T cell survival has not been defined. Here, we present data demonstrating that CD28 costimulation enhances the in vitro survival of activated T cells. One mechanism for this enhancement is the ability of CD28 costimulation to augment the production of IL-2, which acts as an extrinsic survival factor for T cells. In addition, CD28 costimulation augments the intrinsic ability of T cells to resist apoptosis. Although CD28 signal transduction had no effect on Bcl-2 expression, CD28 costimulation was found to augment the expression of Bcl-XL substantially. Transfection experiments demonstrated that this level of Bcl-XL could prevent T cell death in response to TCR cross-linking, Fas cross-linking, or IL-2 withdrawal. These data suggest that an important role of CD28 costimulation is to augment T cell survival during antigen activation.

Publication types

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

MeSH terms

  • Apoptosis
  • Base Sequence
  • CD28 Antigens / metabolism*
  • Cell Survival
  • Cells, Cultured
  • Humans
  • Lymphocyte Activation
  • Molecular Sequence Data
  • Proto-Oncogene Proteins / biosynthesis*
  • Proto-Oncogene Proteins c-bcl-2
  • RNA, Messenger / analysis
  • Second Messenger Systems
  • Signal Transduction
  • T-Lymphocytes / cytology
  • T-Lymphocytes / metabolism*
  • bcl-X Protein

Substances

  • BCL2L1 protein, human
  • CD28 Antigens
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • RNA, Messenger
  • bcl-X Protein