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Blood, 15 September 2006, Vol. 108, No. 6, pp. 1841-1848. Prepublished online as a Blood First Edition Paper on June 1, 2006; DOI 10.1182/blood-2006-02-011981. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2006-02-011981v1 108/6/1841    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 Gross, D.-A. Articles by Davoust, J. Search for Related Content PubMed PubMed Citation Articles by Gross, D.-A. Articles by Davoust, J. Related Collections Immunobiology Transplantation Gene Therapy Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  GENE THERAPY Simple conditioning with monospecific CD4+CD25+ regulatory T cells for bone marrow engraftment and tolerance to multiple gene products David-Alexandre Gross, Pascal Chappert, Marylene Leboeuf, Virginie Monteilhet, Laetitia Van Wittenberghe, Olivier Danos, and Jean Davoust From Genethon, Centre National de la Recherche Scientifique, Unité Mixte de Recherche (CNRS UMR) 8115, Evry, France. A major impediment to gene replacement therapy is immune elimination of genetically modified cells. In principle, this can be dealt with by inducing a strong, specific, and enduring tolerance through engraftment of transgene-modified autologous bone marrow (BM). Because usual myeloablation and/or immunosuppression are risk factors in most pathologies, we assessed the potential of monospecific CD4+CD25+ regulatory T cells (Tregs) to engraft minor-mismatched BM without preconditioning. We found that as few as 5 x 104 Tregs directed to the male DBY protein promote the engraftment of foreign male BM into sex-mismatched female hosts, establishing sustained chimerism in all hematopoeitic compartments. We achieved concomitantly strong tolerance to all foreign antigens expressed in the BM, likely occurring through induction of anergy and/or deletion of antidonor T cells. Chimerism was obtained in thymectomized mice too, underlining the major role of peripheral tolerance mechanisms in our system. This allowed us to engraft gene-modified tissues while preserving full immunocompetence to third-party antigens. Our results demonstrate that very few donor-specific Tregs are effective as the sole conditioning to induce mixed molecular chimerism and long-term tolerance to multiple foreign antigens. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: J.-G. Chai, D. Coe, D. Chen, E. Simpson, J. Dyson, and D. Scott In Vitro Expansion Improves In Vivo Regulation by CD4+CD25+ Regulatory T Cells J. Immunol., January 15, 2008; 180(2): 858 - 869. [Abstract] [Full Text] [PDF] P. Chappert, M. Leboeuf, P. Rameau, D. Stockholm, R. Liblau, O. Danos, J. M. Davoust, and D.-A. Gross Antigen-Driven Interactions with Dendritic Cells and Expansion of Foxp3+ Regulatory T Cells Occur in the Absence of Inflammatory Signals J. Immunol., January 1, 2008; 180(1): 327 - 334. [Abstract] [Full Text] [PDF] L. Weng, J. Dyson, and F. Dazzi Low-intensity transplant regimens facilitate recruitment of donor-specific regulatory T cells that promote hematopoietic engraftment PNAS, May 15, 2007; 104(20): 8415 - 8420. [Abstract] [Full Text] [PDF]

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