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The Journal of Immunology, 2006, 177: 4451-4457.
Copyright © 2006 by The American Association of Immunologists, Inc.

Cell-Autonomous CCL5 Transcription by Memory CD8 T Cells Is Regulated by IL-41

Antoine Marçais, Charles-Antoine Coupet, Thierry Walzer2, Martine Tomkowiak, Raffaella Ghittoni and Jacqueline Marvel3

Institut National de la Santé de la Recherche Médicale, Unité 503, Lyon, France; Institut Fédératif de Recherche 128, BioSciences Lyon-Gerland, Lyon, France; and Université Lyon 1, Villeurbanne, France

Immunological memory is associated with the display of improved effector functions. The maintenance by CD8 memory cells of high levels of untranslated CCL5 mRNA allows these cells to immediately secrete this chemokine upon Ag stimulation. Untranslated mRNA storage is a newly described process supporting the immediate display of an effector function by memory lymphocytes. We have tested the capacity of different cytokines to regulate the memorization of CCL5 by memory CD8 T cells. We found that IL-4 treatment of murine CD8 T cells impairs immediate CCL5 secretion capacity by inhibiting CCL5 mRNA transcription through a STAT6-dependent pathway. The inhibition by IL-4 is reversible, as memory CD8 T cells reconstitute their CCL5 mRNA stores and reacquire their immediate CCL5 secretion capacity when IL-4 is withdrawn. This recovery is cell autonomous because it proceeds in culture medium in the absence of exogenous growth factors, suggesting that CCL5 expression by memory CD8 T cells is a default process. Overall, these results indicate that the expression of CCL5 is an intrinsic property acquired by memory CD8 T cells that is regulated by environmental factors.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

1 This work was supported by institutional grants from Institut National de la Santé et de la Recherche Médicale, Association pour la Recherche contre le Cancer, Ligue Régionale de Lutte Contre le Cancer, Région Rhône-Alpes (Contract 00816045), Université Claude Bernard Lyon 1, and Cancéropole Nationale.

2 Current address: Centre d’Immunologie de Marseille-Luminy, Campus de Luminy, Case 906, Marseille, F-13288 France.

3 Address correspondence and reprint requests to Dr. Jacqueline Marvel, Institut National et la Santé et de la Recherche Medicalé, Unité 503, 21 avenue Tony Garnier, Lyon, France. E-mail address: marvel{at}cervi-lyon.inserm.fr

4 Abbreviations used in this paper: m, murine; RPA, RNase protection assay; WT, wild type.






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