Role of membrane potential in the response of human T lymphocytes to phytohemagglutinin

E. W. Gelfand, R. K. Cheung, G. B. Mills, S. Grinstein

Research output: Contribution to journalArticlepeer-review

55 Scopus citations

Abstract

We have analyzed the role of membrane potential on T cell activation and cell proliferation. Depolarization of T lymphocytes, by increasing the extracellular concentration of K+ during a 1-hr exposure to PHA, results in a marked inhibition of cell proliferation. In parallel, depolarization of T cells prevented the normal increase in [Ca2+](i) seen after PHA binding. In depolarized cells, PHA failed to induce IL 2 secretion, but, in contrast, IL 2 receptor expression was triggered normally and the cells were subsequently responsive to exogenous IL 2. Increasing [Ca2+](i) in depolarized cells with the ionophore ionomycin, or bypassing the requirement for an increase in [Ca2+](i) with TPA, restored the PHA-induced proliferative response in depolarized cells. These data confirm that a membrane potential-sensitive step, namely, Ca2+ influx and the resulting change in [Ca2+](i), is triggered by PHA. The inhibitory effects of depolarization are mediated through the impairment of IL 2 secretion, but not IL 2 receptor expression. T cell proliferation can therefore be regulated by altering membrane potential, which in turn modulates the extent of the change in [Ca2+](i). This study suggests a role for transmembrane potential in the regulation of the T cell proliferative response.

Original languageEnglish (US)
Pages (from-to)527-531
Number of pages5
JournalJournal of Immunology
Volume138
Issue number2
StatePublished - Jan 1 1987
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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