Induction of competence and progression signals in human T lymphocytes by phorbol esters and calcium ionophores

Naoki Kumagai, Stephen H. Benedict, Gordon Mills, Erwin W. Gelfand

Research output: Contribution to journalArticle

40 Citations (Scopus)

Abstract

We have investigated the induction of competence (IL‐2 responsiveness) and progression in human T lymphocyte proliferation triggered by phorbol ester and calcium ionophore. The degree of proliferation induced with the phorbol ester, phorbol 12,13‐dibutyrate (PDB) and the calcium ionophore ionomycin was dependent on the duration of exposure to these agents, with more than 6 h required for obtaining maximum proliferation. Following brief exposure to both agents for 30 min, which did not cause significant proliferation, T cells became competent to proliferate in response to exogenous interleukin 2 (IL‐2). These competent T cells also progressed to DNA synthesis following incubation with PDB in the absence of ionomycin. Induction of competence to proliferate in response to either PDB or IL‐2 was blocked by EGTA, suggesting that transmembrane Ca2+ flux was obligatory at this stage. Since other phorbol esters and synthetic diacylglycerols also stimulated DNA synthesis in competent cells, it is likely that progression was triggered by activation of protein kinase C. Following a brief exposure to PDB and ionomycin, subsequent incubation with PDB induced gene expression and secretion of IL‐2 and augmented the expression of IL‐2 receptors in the competent cells. Thus, we have demonstrated that Ca2+ mobilization is required for rendering T cells competent to express functional IL‐2 receptors, to produce IL‐2 in response to subsequent incubation with PDB, and that sustained activation of protein kinase C seems necessary for IL‐2 production and subsequent progression of competent T cells to DNA synthesis.

Original languageEnglish (US)
Pages (from-to)329-336
Number of pages8
JournalJournal of Cellular Physiology
Volume137
Issue number2
DOIs
StatePublished - Jan 1 1988
Externally publishedYes

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T-cells
Calcium Ionophores
Phorbol Esters
Mental Competency
Interleukin-2
T-Lymphocytes
Ionomycin
Interleukin-2 Receptors
Protein Kinase C
DNA
Chemical activation
Egtazic Acid
Diglycerides
Gene expression
Fluxes
Gene Expression

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Cell Biology

Cite this

Induction of competence and progression signals in human T lymphocytes by phorbol esters and calcium ionophores. / Kumagai, Naoki; Benedict, Stephen H.; Mills, Gordon; Gelfand, Erwin W.

In: Journal of Cellular Physiology, Vol. 137, No. 2, 01.01.1988, p. 329-336.

Research output: Contribution to journalArticle

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