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Blood, 1 July 2007, Vol. 110, No. 1, pp. 211-219. Prepublished online as a Blood First Edition Paper on March 13, 2007; DOI 10.1182/blood-2006-10-052506. This Article Full Text Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2006-10-052506v1 110/1/211    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Hamdi, H. Articles by Emilie, D. Search for Related Content PubMed PubMed Citation Articles by Hamdi, H. Articles by Emilie, D. Related Collections Immunobiology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Induction of antigen-specific regulatory T lymphocytes by human dendritic cells expressing the glucocorticoid-induced leucine zipper Haifa Hamdi1,2, Véronique Godot1,2, Marie-Christine Maillot1, Maria Victoria Prejean1, Nicolas Cohen1,2, Roman Krzysiek1,3, François M. Lemoine4,6, Weiping Zou7, and Dominique Emilie1,3 1 Institut National de la Santé et de la Recherche Médicale, U764, Clamart, France; 2 Université Paris-Sud, Faculté de médecine Paris Sud, Institut Fédératif de Recherche 13, Clamart, France; 3 Assistance Publique–Hôpitaux de Paris, Hôpital Antoine Béclère, Service de Microbiologie–Immunologie Biologique, Clamart, France; 4 Centre National de la Recherche Scientifique, Unité Mixte de Recherche 7087, Paris, France; 5 Université Pierre et Marie Curie, Institut Fédératif de Recherche 113, Paris, France; 6 Assistance Publique–Hôpitaux de Paris, Groupe Hospitalier Pitié-Salpêtrière, Service de Biothérapie, Paris, France; 7 Department of Surgery, University of Michigan School of Medicine, Ann Arbor Dendritic cells (DCs) determine whether antigen presentation leads to immune activation or to tolerance. Tolerance-inducing DCs (also called regulatory DCs) act partly by generating regulatory T lymphocytes (Tregs). The mechanism used by DCs to switch toward regulatory DCs during their differentiation is unclear. We show here that human DCs treated in vitro with glucocorticoids produce the glucocorticoid-induced leucine zipper (GILZ). Antigen presentation by GILZ-expressing DCs generates CD25highFOXP3+CTLA-4/CD152+ and interleukin-10–producing Tregs inhibiting the response of CD4+ and CD8+ T lymphocytes. This inhibition is specific to the antigen presented, and only proliferating CD4+ T lymphocytes express the Treg markers. Interleukin-10 is required for Treg induction by GILZ-expressing DCs. It is also needed for the suppressive function of Tregs. Antigen-presenting cells from patients treated with glucocorticoids generate interleukin-10–secreting Tregs ex vivo. These antigen-presenting cells produce GILZ, which is needed for Treg induction. Therefore, GILZ is critical for commitment of DCs to differentiate into regulatory DCs and to the generation of antigen-specific Tregs. This mechanism may contribute to the therapeutic effects of glucocorticoids. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: K. R. Kalli, C. J. Krco, L. C. Hartmann, K. Goodman, M. J. Maurer, C. Yu, E. M. Johnson, C. L. Erskine, M. L. Disis, P. J. Wettstein, et al. An HLA-DR-Degenerate Epitope Pool Detects Insulin-like Growth Factor Binding Protein 2-Specific Immunity in Patients with Cancer Cancer Res., June 15, 2008; 68(12): 4893 - 4901. [Abstract] [Full Text] [PDF]

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