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Prepublished online as a Blood First Edition Paper on July 12, 2002; DOI 10.1182/blood-2002-01-0235. This Article Full Text (PDF) All Versions of this Article: 2002-01-0235v1 100/9/3408    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 Young, K. J Articles by Zhang, L. Search for Related Content PubMed PubMed Citation Articles by Young, K. J Articles by Zhang, L. Social Bookmarking                   What's this? Submitted January 25, 2002 Accepted June 10, 2002 Donor-lymphocyte infusion induces tolerance by activating systemic and graft-infiltrating double negative regulatory T cells Kevin J Young, Liming Yang, M. James Philips, and Li Zhang* Multi Organ Transplantation Program, Toronto General Research Institute, University Health Network, Toronto, Ontario, Canada; Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada Multi Organ Transplantation Program, Toronto General Research Institute, University Health Network, Toronto, Ontario, Canada; Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada; Immunology, University of Toronto, Toronto, Ontario, Canada * Corresponding author; email: lzhang{at}transplantunit.org. Pretransplantation donor lymphocyte infusion (DLI) can lead to specific tolerance to allografts in mice, primates and humans. We and others have demonstrated a role for regulatory T cells in DLI-induced donor specific transplantation tolerance. It is nonetheless unclear how regulatory T cells are activated, and where they execute their function. Here we demonstrate, in both transgenic and normal mice, that pretransplant DLI is required for the activation of ß-T cell receptor (TCR)+CD3+CD4-CD8- double negative (DN) regulatory T cells in the periphery of recipient animals. More interestingly, DLI promotes the DN regulatory T cells to preferentially migrate to donor-specific allogeneic skin grafts, and form a majority of graft infiltrating T cells in accepted skin allografts. Furthermore, both recipient-derived peripheral as well as graft infiltrating DN T cells are able to suppress and kill anti-donor CD8+ T cells in an antigen-specific manner. These data indicate that DLI may induce donor-specific transplantation tolerance by activating recipient DN regulatory T cells in the periphery, and by promoting the migration of regulatory T cells to the donor-specific allogeneic skin grafts. Our results also demonstrate that DN regulatory T cells can eliminate anti-donor T cells both systemically and locally, suggesting that graft-infiltrating T cells can be beneficial to graft survival. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: J. Li, J. Park, D. Foss, and I. Goldschneider Thymus-homing peripheral dendritic cells constitute two of the three major subsets of dendritic cells in the steady-state thymus J. Exp. Med., March 16, 2009; 206(3): 607 - 622. [Abstract] [Full Text] [PDF] F. Casiraghi, N. Azzollini, P. Cassis, B. Imberti, M. Morigi, D. Cugini, R. A. Cavinato, M. Todeschini, S. Solini, A. Sonzogni, et al. Pretransplant Infusion of Mesenchymal Stem Cells Prolongs the Survival of a Semiallogeneic Heart Transplant through the Generation of Regulatory T Cells J. Immunol., September 15, 2008; 181(6): 3933 - 3946. [Abstract] [Full Text] [PDF] M. S. Ford McIntyre, K. J. Young, J. 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