HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Meiffren, G. Articles by Faure, M. Search for Related Content PubMed PubMed Citation Articles by Meiffren, G. Articles by Faure, M.

Cutting Edge: Abortive Proliferation of CD46-Induced Tr1-Like Cells due to a Defective Akt/Survivin Signaling Pathway¹

Institut National de la Santé et de la Recherche Médicale Unité 503–IFR 128-BioSciences Lyon-Gerland–Université Claude-Bernard-Lyon 1, Lyon, France

T regulatory cell 1 (Tr1) are low proliferating peripherally induced suppressive T cells. Engaging CD3 and CD46 on human CD4⁺ T cells induces a Tr1-like phenotype. In this study, we report that human Tr1-like cells do not sustain proliferation over time. The weak proliferation of these cells results first from their inability to sustain expression of various cell cycle-associated proteins, to efficiently degrade the inhibitor of cell cycle progression p27/Kip1 and, as a consequence, in their accumulation in the G₀-G₁ phase. Also, the reduced proliferation of Tr1-like cells results from their increased sensitivity to death as they divide, through a mechanism that is neither Fas-mediated nor Bcl2/Bcl-xL related. Both properties, impaired cell cycle and death sensitivity, are explained by a specific defective activation of Akt that impairs the expression of Survivin. Thus, our results show that CD3/CD46-induced Tr1-like cells die through a process of abortive proliferation.

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 grants from Institut National de la Santé et de la Recherche Médicale, Université Claude-Bernard-Lyon 1, and Cancéropôle.

² Address correspondence and reprint requests to Dr. Mathias Faure, Institut National de la Santé et de la Recherche Médicale U503–IFR 128 BioSciences Lyon-Gerland–Université Claude-Bernard-Lyon1; 21, Avenue Tony Garnier; 69365 Lyon Cedex 7, France. E-mail address: faure{at}cervi-lyon.inserm.fr

³ Abbreviations used in this paper: Tr1, T-regulatory cell 1; Cdk2, cyclin-dependent kinase 2; PY, pyronin Y; TBP, TATA box-binding protein; 7-AAD, 7-aminoactinomycin D.