Inunature thyrnocytes become sensitive to calcium-mediated apoptosis with the onset of CD8, CD4, and the T cell receptor expression: A role for bcl-2?

Sofija Andjelić, Nada Jain, Janko Nikolić-Žugić

Research output: Contribution to journalArticlepeer-review

34 Scopus citations

Abstract

During intrathymic negative selection by clonal deletion, crosslinking of the T cell receptor (TCR) induces cell death by delivering an apoptotic signal(s) to the nucleus along a calcium-dependent pathway. We investigated the reactivity of early precursor-containing thymocytes to Ca2+-induced signals, and discovered a breakpoint in their sensitivity to calcium-mediated cell death (CMCD). CD25+ CD84 TCK (triple negative [TN]) thymocytes stimulated with a calcium ionophore maintain their viability and precursor activity. By contrast, their immediate progeny, CD25CD8lo4loTCRαβlo (triple low [TL]) cells react to calcium elevation by abrogation of precursor activity and apoptotic cell death. This developmental difference is specific for CMCD, since both CD25+ TN and CD25-TL cells are susceptible to steroid-induced apoptosis. The presence of bcl-2 mRNA correlates directly to the resistance to CMCD- CD25+ TN cells express it and CD25-TL cells do not. These experiments show that thymocytes become sensitive to Ca 2+-induced apoptosis as soon as they begin to express molecules that mediate thymic sdection, and suggest that a concomitant downregulation of bcl-2 may mediate this phenomenon.

Original languageEnglish (US)
Pages (from-to)1745-1751
Number of pages7
JournalJournal of Experimental Medicine
Volume178
Issue number5
DOIs
StatePublished - Nov 1 1993
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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