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Blood, 15 January 2004, Vol. 103, No. 2, pp. 732-739. Prepublished online as a Blood First Edition Paper on September 25, 2003; DOI 10.1182/blood-2003-02-0643. This Article Full Text 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 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 Kim, Y.-M. Articles by Sykes, M. Search for Related Content PubMed PubMed Citation Articles by Kim, Y.-M. Articles by Sykes, M. Related Collections Immunobiology Transplantation Immunotherapy Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  TRANSPLANTATION Graft-versus-host-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 From the Transplantation Biology Research Center, Bone Marrow Transplantation Section, Massachusetts General Hospital/Harvard Medical School, Boston, MA; Biotransplant, Inc, Medford, MA; and Schepens Eye Institute, Harvard Medical School, Boston, MA. Murine mixed hematopoietic chimerism can be achieved following nonmyeloablative conditioning with cyclophosphamide, T cell–depleting monoclonal antibodies, and thymic irradiation. Donor lymphocyte infusions (DLIs) 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 DLIs in converting mixed to full donor chimerism in a fully major histocompatibility complex–mismatched strain combination. Whereas DLIs 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 DLIs led to complete loss of donor chimerism in a high proportion (54%) of recipients compared with CD4-plus CD8-depleted DLIs (15%) or CD4-depleted DLIs (0%) (P < .05). DLIs administered at early time points after BMT (eg, day 21) also precipitated rejection of donor marrow by recipient T cells, in association with donor CD4 cell expansion and high production of interleukin 2 (IL-2), IL-4, and interferon-. Thus, DLIs can paradoxically induce marrow rejection by residual host T cells. These results have implications for the timing of and use of subset depletion of DLIs in recipients of nonmyeloablative transplants. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: Y. Suzuki, Y. Adachi, K. Minamino, Y. Zhang, M. Iwasaki, K. Nakano, Y. Koike, and S. Ikehara A New Strategy for Treatment of Malignant Tumor: Intra-Bone Marrow-Bone Marrow Transplantation Plus CD4- Donor Lymphocyte Infusion Stem Cells, March 1, 2005; 23(3): 365 - 370. [Abstract] [Full Text] [PDF] 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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