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Blood, 1 June 2004, Vol. 103, No. 11, pp. 4216-4221. Prepublished online as a Blood First Edition Paper on February 19, 2004; DOI 10.1182/blood-2004-01-0005. This Article Full Text (PDF) All Versions of this Article: 2004-01-0005v1 103/11/4216    most recent Alert me when this article is cited Alert me if a correction is posted 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 Joffre, O. Articles by van Meerwijk, J. P Search for Related Content PubMed PubMed Citation Articles by Joffre, O. Articles by van Meerwijk, J. P Related Collections Related Article in Blood Online Social Bookmarking                   What's this? Submitted January 5, 2004 Accepted February 2, 2004 Induction of antigen specific tolerance to bone marrow allografts with CD4+CD25+ T lymphocytes Olivier Joffre, Nathalie Gorsse, Paola Romagnoli, Denis Hudrisier, and Joost P van Meerwijk* Tolerance and Autoimmunity section, INSERM U563, Toulouse, France Tolerance and Autoimmunity section, INSERM U563, Toulouse, France; UFR-SVT, University Toulouse III, Toulouse, France Tolerance and Autoimmunity section, INSERM U563, Toulouse, France; UFR-SVT, University Toulouse III, Toulouse, France; Institut Universitaire de France, France * Corresponding author; email: joost.van-meerwijk{at}toulouse.inserm.fr. Thymus-derived regulatory T lymphocytes of CD4+CD25+ phenotype regulate a large variety of beneficial and deleterious immune-responses and can inhibit lethal graft-versus-host disease in rodents. In vitro, CD4+CD25+ T cells require specific MHC/peptide ligands for their activation, but once activated they act in an antigen-non-specific manner. In vivo, regulatory T cells are also activated in an antigen-specific fashion, but nothing is known about antigen-specificity of their suppressor effector function. Here we show that CD4+CD25+ regulatory T lymphocytes isolated from naive mice and activated in vitro with allogeneic APC, induced specific long-term tolerance to bone-marrow grafts disparate for major and minor histocompatibility antigens : Whereas "target" bone-marrow was protected, third-party bone-marrow was rejected. Importantly, in mice injected with a mix of target and third-party bone-marrows, protection and rejection processes took place simultaneously. These results indicate that CD4+CD25+ regulatory T cells can act in an antigen-specific manner in vivo. Our results suggest that CD4+CD25+ regulatory T cells could in the future be used in clinical settings to induce specific immunosuppression. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Alloantigen-specific regulatory T cells Bryon Johnson Blood 2004 103: 4000. [Full Text] [PDF] This article has been cited by other articles: L. C. Chen, J. C. Delgado, P. E. Jensen, and X. Chen Direct Expansion of Human Allospecific FoxP3+CD4+ Regulatory T Cells with Allogeneic B Cells for Therapeutic Application J. Immunol., September 15, 2009; 183(6): 4094 - 4102. [Abstract] [Full Text] [PDF] B. Blanco, J. A. Perez-Simon, L. I. Sanchez-Abarca, T. Caballero-Velazquez, S. Gutierrez-Cossio, P. Hernandez-Campo, M. Diez-Campelo, C. Herrero-Sanchez, C. Rodriguez-Serrano, C. Santamaria, et al. 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