Role of membrane potential in the response of human T lymphocytes to phytohemagglutinin.
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.
D002118:Calcium / Q000502:physiology*; D004987:Ethers / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D007376:Interleukin-2 / Q000378:metabolism; D015759:Ionomycin; D008213:Lymphocyte Activation / Q000187:drug effects; D008564:Membrane Potentials / Q000187:drug effects; D010835:Phytohemagglutinins / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D011971:Receptors, Immunologic / Q000378:metabolism; D015375:Receptors, Interleukin-2; D013601:T-Lymphocytes / Q000187:drug effects / Q000502:physiology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D004987:Ethers; D007376:Interleukin-2; D010835:Phytohemagglutinins; D011971:Receptors, Immunologic; D015375:Receptors, Interleukin-2; D015759:Ionomycin; D011189:Potassium Chloride; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium