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

Alan D Guerrero, Robert L Welschhans, Min Chen, Jin Wang

Research output: Contribution to journalArticle

18 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)168-73
Number of pages6
JournalJournal of Immunology
Volume190
Issue number1
DOIs
StatePublished - Jan 1 2013

Keywords

  • Animals
  • Apoptosis Regulatory Proteins
  • Cell Death
  • Cell Line
  • Cell Survival
  • Humans
  • Hydrolysis
  • Lymphocyte Activation
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred MRL lpr
  • Multigene Family
  • Primary Cell Culture
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • Receptor Cross-Talk
  • Receptors, Antigen, T-Cell
  • T-Lymphocyte Subsets
  • bcl-X Protein
  • Comparative Study
  • Journal Article
  • Research Support, N.I.H., Extramural

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