CAML regulates Bim-dependent thymocyte death

C. E. Edgar, L. D. Lindquist, D. L. McKean, A. Strasser, R. J. Bram

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

Appropriate control of apoptosis during T lymphocyte differentiation is critical for destruction of T cells bearing potentially autoreactive or useless immuno-receptors and for survival of those T cells bearing antigen receptors that may recognize foreign proteins. Despite the well-established importance of thymocyte survival, the exact signals regulating thymocyte apoptosis have not been fully elucidated. Here, we show that thymocytes lacking the endoplasmic reticulum protein calcium-modulating cyclophilin ligand (CAML) failed to undergo normal T-cell development and exhibited dramatically increased rates of apoptosis. In vitro, CAML-deficient thymocytes accumulated high levels of reactive oxygen species (ROS) and underwent abnormally accelerated death in response to several cytotoxic stimuli, including treatment with etoposide, cytokine deprivation, or Fas ligation. Although neither p53 deletion nor loss of Fas rescued the survival and continued development of CAML-deficient thymocytes, removal of the pro-apoptotic BH3-only Bcl-2 family member Bim significantly restored their survival. This work reveals CAML to be a critically important regulator of ROS- and Bim-dependent thymocyte death.

Original languageEnglish (US)
Pages (from-to)1566-1576
Number of pages11
JournalCell Death and Differentiation
Volume17
Issue number10
DOIs
StatePublished - Oct 2010

Keywords

  • Bim
  • CAML
  • ROS
  • T-cell development

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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