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Sustained and dynamic inositol lipid metabolism inside and outside the immunological synapse

Nature Immunology volume 3, pages 1082–1089 (2002)Cite this article

Abstract

T cell activation is triggered by several hours of contact with peptide–major histocompatibility (MHC) complexes on the surface of antigen-presenting cells (APCs). The nature and location of the sustained signal transduction pathways required for T cell activation are unknown. We show here that the production of phosphatidylinositol(3,4,5)triphosphate (PIP3) was dynamically sustained for hours as T cells responded to antigen. In addition, sustained elevation of PIP3 was essential for T cell proliferation. There was PIP3 accumulation in the T cell–APC contact zone and at the antipodal pole of the cell. The immune synapse is thus not the sole site of sustained signal transduction in activated T cells.

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Figure 1: Generation of mice expressing GFP–PKB-PH.
Figure 2: Distribution of GFP–PKB-PH in resting T cells and translocation in response to PI3K activation.
Figure 3: Localization of GFP–PKB-PH in activated T cells.
Figure 4: Membrane localization of GFP–PKB-PH is sustained in antigen-activated T cells.
Figure 5: Membrane distribution of PKB GFP-PH.
Figure 6: Sustained PI3K activity in antigen-activated T cells.
Figure 7: PI3K requirement for T cell activation.

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Acknowledgements

We thank I. Rosewell for injection of transgenic constructs; T. Grafton, S. Hoskins, J. Bee and G. Hutchinson for animal care; and P. Jordan, D. Zicha and J. Monypenny for help with confocal microscopy. Supported by the Fondation pour la Recherche Medicale (M. G.) and Cancer Research UK (P. S. C. and D. A. C.).

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  1. Lymphocyte Activation Laboratory, Cancer Research UK London Research Institute, Lincoln's Inn Fields Laboratories, 44 Lincoln's Inn Fields, London, WC2A 3PX, UK

    Patrick S. Costello, Maighread Gallagher & Doreen A. Cantrell

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Correspondence to Doreen A. Cantrell.

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Costello, P., Gallagher, M. & Cantrell, D. Sustained and dynamic inositol lipid metabolism inside and outside the immunological synapse. Nat Immunol 3, 1082–1089 (2002). https://doi.org/10.1038/ni848

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