Cleavage of anti-apoptotic Bcl-2 family members after TCR stimulation contributes to the decision between T cell activation and apoptosis

J Immunol. 2013 Jan 1;190(1):168-73. doi: 10.4049/jimmunol.1201610. Epub 2012 Nov 30.


Engagement of the TCR induces activation-induced cell death (AICD) of T cells that have been previously stimulated. However, a portion of these T cells can survive and undergo further activation. The molecular mechanism that decides whether a T cell will live or die after TCR re-engagement is unclear. We found that cross-linking of TCR in preactivated primary mouse T cells led to the cleavage of anti-apoptotic Bcl-2 and Bcl-xL in dying cells. Cleavage-resistant Bcl-2 and Bcl-xL were more efficient than their wild-type counterparts in the inhibition of apoptosis in primary mouse T cells and in the H9 T cell line after TCR cross-linking. In contrast, the surviving T cells after TCR re-engagement displayed upregulation of Bcl-xL, and knockdown of Bcl-xL promoted AICD. This indicates that caspase-mediated cleavage of anti-apoptotic Bcl-2 or Bcl-xL facilitates AICD in T cells, whereas upregulation of Bcl-xL promotes T cell survival and allows further T cell activation. Our data suggest that cleavage of anti-apoptotic Bcl-2 and Bcl-xL contributes to the decision between T cell activation and apoptosis after TCR re-engagement.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Apoptosis Regulatory Proteins / metabolism*
  • Apoptosis Regulatory Proteins / physiology
  • Cell Death / immunology
  • Cell Line
  • Cell Survival / immunology
  • Humans
  • Hydrolysis
  • Lymphocyte Activation / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred MRL lpr
  • Multigene Family / immunology*
  • Primary Cell Culture
  • Proto-Oncogene Proteins / metabolism*
  • Proto-Oncogene Proteins / physiology
  • Proto-Oncogene Proteins c-bcl-2 / metabolism*
  • Proto-Oncogene Proteins c-bcl-2 / physiology
  • Receptor Cross-Talk / immunology
  • Receptors, Antigen, T-Cell / metabolism
  • Receptors, Antigen, T-Cell / physiology*
  • T-Lymphocyte Subsets / cytology
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocyte Subsets / metabolism
  • bcl-X Protein / metabolism*
  • bcl-X Protein / physiology


  • Apoptosis Regulatory Proteins
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • Receptors, Antigen, T-Cell
  • bcl-X Protein
  • Bcl2 protein, mouse