Killing of immature CD4+CD8+ thymocytes in vivo by anti‐CD3 or 5′‐(N‐ethyl)‐carboxamido‐adenosine is blocked by glucocorticoid receptor antagonist RU‐486

Mikael Jondal, Sam Okret, David McConkey

Research output: Contribution to journalArticle

Abstract

Negative selection in thymus occurs by apoptosis in CD4+CD81 cells. These immature thymocytes are readily killed, both in vitro and in vivo, by glucocorticoid treatment. Increased levels of intracellular cAMP in vitro also induce apoptosis of thymocytes and T cell receptor (TcR) stimulation potentiate cAMP responses through receptors linked to adenylic cyclase. Presently, we have tested the possibility that TcR‐mediated apoptosis in vivo may require the glucocorticoid receptor (GR) as a downstream, intracellular mediator. Use of the GR antagonist RU‐486, 24 h before and simultaneous with, anti‐CD3 or 5′‐(N‐ethyl)‐carboxamide‐adenosine (NECA) treatment, resulted in a selective inhibition of CD4+CD8+ thymocyte death. In addition, a low dose of glucocorticoid potentiated thymocyte death induced by anti‐CD3 monoclonal antibodies. These data support a model in which thymic negative selection depends on a defined set of transduction signals which potentiate the GR to become responsive to endogenous levels of glucocorticoid.

Original languageEnglish (US)
Pages (from-to)1246-1250
Number of pages5
JournalEuropean Journal of Immunology
Volume23
Issue number6
DOIs
StatePublished - Jun 1993
Externally publishedYes

Keywords

  • Apoptosis
  • Glucocorticoid
  • T cell receptor
  • Thymocyte
  • cAMP

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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