Agents that elevate cAMP stimulate DNA fragmentation in thymocytes

D. J. McConkey, S. Orrenius, M. Jondal

Research output: Contribution to journalArticle

Abstract

Increases in the cAMP level are often inhibitory in mature T lymphocytes and may be involved in the development of tolerance to self Ag. In this report, agents inducing an increase in the cAMP level by independent mechanisms were found to stimulate DNA fragmentation, characteristic of a suicide program known as apoptosis, in isolated thymocytes. Data obtained with cAMP analogs known to act synergistically to stimulate protein kinase A suggested that the latter directly mediated endonuclease activation. Agents previously shown to stimulate protein kinase C and to inhibit Ca2+-dependent, TCR-mediated thymocyte apoptosis, including IL-1, also blocked both DNA fragmentation and cell death in response to cAMP, suggesting interactions ('cross-talk') between the two protein kinase systems. As it has been proposed that apoptosis mediates negative cell selection in the thymus, our results indicate that cAMP may play a role in the development of functional mature T lymphocytes.

Original languageEnglish (US)
Pages (from-to)1227-1230
Number of pages4
JournalJournal of Immunology
Volume145
Issue number4
StatePublished - Jan 1 1990
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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