Differential regulation of bcl-2 and bcl-x by CD3, CD28, and the IL-2 receptor in cloned CD4+ helper T cells: A model for the long-term survival of memory cells

Daniel L. Mueller, Suzanne Seiffert, Wei Fang, Timothy W. Behrens

Research output: Contribution to journalArticle

110 Scopus citations

Abstract

In this study, we examined the molecular signals that control apoptosis in cloned CD4+ helper T cells. Resting T cells were highly resistant to spontaneous death in the absence of exogenous stress, and they expressed low levels of bcl-x protein and no detectable bcl-2. Upon exposure to gamma radiation, resting cells rapidly underwent apoptotic death. Incubation with IL-2 prevented this cell death and led to a large increase in bcl-2 protein expression and only a modest up-regulation in bcl-x. The combination of anti- CD3 and anti-CD28 mAbs was also effective in protecting the cells against radiation-induced apoptosis; however, this protection was associated predominantly with bcl-x up-regulation, and only a small induction of bcl-2 protein was observed. Finally, cyclosporin A blocked both IL-2 secretion and bcl-2 induction in response to CD3 plus CD28 stimulation, suggesting a role for endogenous lymphokine production in the induction of bcl-2. These data support a model in which memory T cells remain resistant to apoptosis because intermittent contact with Ag-bearing APC and IL-2R occupancy result in the expression of the life-proteins bcl-2 and bcl-x.

Original languageEnglish (US)
Pages (from-to)1764-1771
Number of pages8
JournalJournal of Immunology
Volume156
Issue number5
StatePublished - Mar 1 1996

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