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Early steps of lymphocyte activation bypassed by synergy between calcium ionophores and phorbol ester

Nature volume 313, pages 318–320 (1985)Cite this article

Abstract

Although it has been proposed that the activation of T lymphocytes is mediated by an early rise in cytosolic calcium concentration1–4, it has not been possible to mimic antigen- or mitogen-induced mouse lymphocyte activation by calcium ionophores that bypass receptor-mediated processes1,3. There is now evidence from other systems that the rise in cytosolic calcium which follows receptor triggering is preceded by the breakdown of phosphatidylinositol bisphosphate into 1,2-diacylglycerol and inositol trisphosphate (for reviews see refs 5–8). The latter is known to cause release of calcium from intracellular stores8. The cellular target for the former is now widely accepted to be protein kinase C (ref. 6). Therefore, ligand-induced cellular response follows a rise in cytosolic calcium concentration and protein kinase C activation. Here we confirm that the calcium ionophores A23187 and ionomycin do not activate mouse T lymphocytes. However, either one in combination with the phorbol ester 12-O-tetradecanoylphorbol 13-acetate (TPA), which is structurally related to 1,2-diacylglycerol, induces in lymphoid cell populations the expression of receptors for interleukin-2 (IL-2), the secretion of IL-2 and cell proliferation as measured by 3H-thymidine uptake. The growth-promoting effect of IL-29,10 on an exogenous IL-2-dependent clone could not be substituted for by ionomycin either alone or with TPA. Thus, the combination of calcium ionophores and TPA bypasses the requirement for antigen- or lectin-induced signal at the onset of lymphocyte activation.

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Author notes

  1. Alemseged Truneh

    Present address: Department of Immunology, Smith, Kline & French Laboratories, L102, 1500 Spring Gdn St, Philadelphia, Pennsylvania, 19101, USA

Authors and Affiliations

  1. Centre d'Immunologie ISERM-CNRS de Marseille-Luminy, Case 906, 13288, Marseille, Cédex 9, France

    Alemseged Truneh, Françoise Albert, Pierre Golstein & Anne-Marie Schmitt-Verhulst

  2. Faculté de Pharmacie, Université d'Aix-Marseille II, 27, Boulevard Jean Moulin, 13385, Marseille, Cedex 5, France

    Alemseged Truneh, Françoise Albert, Pierre Golstein & Anne-Marie Schmitt-Verhulst

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  1. Alemseged Truneh
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  2. Françoise Albert
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  4. Anne-Marie Schmitt-Verhulst
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Truneh, A., Albert, F., Golstein, P. et al. Early steps of lymphocyte activation bypassed by synergy between calcium ionophores and phorbol ester. Nature 313, 318–320 (1985). https://doi.org/10.1038/313318a0

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