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Prepublished online as a Blood First Edition Paper on September 25, 2003; DOI 10.1182/blood-2003-02-0643. This Article Full Text (PDF) All Versions of this Article: 2003-02-0643v1 103/2/732    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 Kim, Y.-M. Articles by Sykes, M. Search for Related Content PubMed PubMed Citation Articles by Kim, Y.-M. Articles by Sykes, M. Social Bookmarking                   What's this? Submitted March 5, 2003 Accepted September 15, 2003 Graft-versus-host (GVH)-reactive donor CD4 cells can induce T-cell-mediated rejection of the donor marrow in mixed allogeneic chimeras prepared with nonmyeloablative conditioning Yong-Mi Kim, Markus Y Mapara, Julian D Down, Kevin W Johnson, Florence Boisgerault, Yoshinobu Akiyama, Gilles Benichou, Michele Pelot, Guiling Zhao, and Megan Sykes* Transplantation Biology Research Center/Bone Marrow Transplantation Section, Massachusetts General Hospital, Boston, MA, USA BioTransplant Inc., Medford, M A, USA Schepens Eye Institute, Boston, MA, USA University Medical Center Charite/Department of Hematology and Oncology, Humboldt University, Humboldt, Germany Unite de Biologie des Regulations Immunitaires, Institut Pasteur, Paris, France Department of Surgery, Massachusetts General Hospital, Boston, MA, USA * Corresponding author; email: megan.sykes{at}tbrc.mgh.harvard.edu. Murine mixed hematopoietic chimerism can be achieved following non-myeloablative conditioning with cyclophosphamide, T cell depleting mAbs and thymic irradiation. Donor lymphocyte infusions (DLI) 35 days after bone marrow transplantation (BMT) convert mixed to full donor chimerism and mediate graft-versus-lymphoma effects without graft-versus-host disease. We evaluated the role of T-cell subsets in DLI in converting mixed to full donor chimerism in a fully MHC-mismatched strain combination. While DLI administered on Day 35 converted 100% of mixed chimeras to full donor chimerism, conversion was less frequent when either CD4 or CD8 cells were depleted, indicating that both subsets contribute to the conversion. Surprisingly, administration of CD8-depleted DLI led to complete loss of donor chimerism in a high proportion (54%) of recipients compared to CD4 plus CD8-depleted DLI (15%) or CD4-depleted DLI (0%) (P<0.05). DLI administered at early time points post-BMT (e.g. Day 21) also precipitated rejection of donor marrow by recipient T cells, in association with donor CD4 cell expansion and high production of IL-2, IL-4 and IFN-. Thus, DLI can paradoxically induce marrow rejection by residual host T cells. These results have implications for the timing of and use of subset depletion of DLI in recipients of non-myeloablative transplants. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: Y. Liang, T. Huang, C. Zhang, I. Todorov, M. Atkinson, F. Kandeel, S. Forman, and D. Zeng Donor CD8+ T cells facilitate induction of chimerism and tolerance without GVHD in autoimmune NOD mice conditioned with anti-CD3 mAb Blood, March 1, 2005; 105(5): 2180 - 2188. [Abstract] [Full Text] [PDF]

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