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New Molecular and Cellular Mechanisms of Tolerance: Tolerogenic Actions of IL-2

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Suppression and Regulation of Immune Responses

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1371))

Abstract

Interleukin-2 (IL-2) is an old molecule with brand new functions. Indeed, IL-2 has been first described as a T-cell growth factor but recent data pointed out that its main function in vivo is the maintenance of immune tolerance. Mechanistically, IL-2 is essential for the development and function of CD4+ Foxp3+ regulatory T cells (Treg cells) that are essential players in the control of immune responded to self, tumors, microbes and grafts. Treg cells are exquisitely sensitive to IL-2 due to their constitutive expression of the high affinity IL-2 receptor (IL-2R) and the new paradigm suggests that low-doses of IL-2 could selectively boost Treg cells in vivo. Consequently, a growing body of clinical research is aiming at using IL-2 at low doses as a tolerogenic drug to boost endogenous Treg cells in patients suffering from autoimmune or inflammatory conditions. In this manuscript, we briefly review IL-2/IL-2R biology and the role of IL-2 in the development, maintenance, and function of Treg cells; and also its effects on other immune cell populations such as CD4+ T helper cells and CD8+ memory T cells. Then, focusing on type 1 diabetes, we review the preclinical studies and clinical trials supporting the use of low-doses IL-2 as a tolerogenic immunotherapy. Finally, we discuss the limitations and future directions for IL-2 based immunotherapy.

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Authors and Affiliations

  1. INSERM U932, 26 rue d’Ulm, 75005, Paris, France

    Louis Pérol & Eliane Piaggio

  2. Institut Curie, Section Recherche, 26 rue d’Ulm, 75005, Paris, France

    Louis Pérol & Eliane Piaggio

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  1. Louis Pérol
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  1. INSERM UMR 643, Nantes, France

    Maria Cristina Cuturi

  2. INSERM UMR 643, Nantes, France

    Ignacio Anegon

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Pérol, L., Piaggio, E. (2016). New Molecular and Cellular Mechanisms of Tolerance: Tolerogenic Actions of IL-2. In: Cuturi, M., Anegon, I. (eds) Suppression and Regulation of Immune Responses. Methods in Molecular Biology, vol 1371. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-3139-2_2

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  • DOI: https://doi.org/10.1007/978-1-4939-3139-2_2

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