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Blood, 15 May 2007, Vol. 109, No. 10, pp. 4564-4574. Prepublished online as a Blood First Edition Paper on January 16, 2007; DOI 10.1182/blood-2006-09-048124. This Article Full Text (PDF) Supplemental Figure All Versions of this Article: blood-2006-09-048124v1 109/10/4564    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 Durakovic, N. Articles by Luznik, L. Search for Related Content PubMed PubMed Citation Articles by Durakovic, N. Articles by Luznik, L. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted September 27, 2006 Accepted January 6, 2007 Factors governing the activation of adoptively transferred donor T-cells infused after allogeneic bone marrow transplantation in the mouse Nadira Durakovic, Vedran Radojcic, Mario Skarica, Karl B Bezak, Jonathan D. Powell, Ephraim J. Fuchs, and Leo Luznik* Divisions of Hematologic Malignancies, and Cancer Immunology, and Hematopoiesis, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD, United States * Corresponding author; email: luznile{at}jhmi.edu. Murine models of bone marrow transplantation were used to study the mechanisms governing the activation of donor lymphocyte infusions (DLIs) manifesting as lymphohematopoietic-graft-versus-host (LH-GVH) and graft-versus-leukemia (GVL) reactivities. We demonstrate here that established mixed chimerism influences the potency of DLI-mediated alloreactivity only in MHC-mismatched but not -matched setting. In the MHC-matched setting, high levels (40%) of residual host chimerism correlated negatively with DLI-mediated alloreactivity irrespective of the timing of their administration, the donor's previous sensitization to host antigens, or the level of residual host APCs. In vivo administration of Toll-like receptor (TLR) ligands was required to maximize DLI-mediated LH-GVH and GVL reactivities in chimeras with low levels (15%) of residual host chimerism. In contrast, coadministration of DLI with APC activators was insufficient to augment their LH-GVH response in the presence of high levels of host chimerism unless the host's T-cells were transiently depleted. Together, these results show the cardinal influence of donor-host incompatibility on DLI-mediated GVH responses, and suggest that in MHC-matched chimeras, the induction of optimal alloreactivity requires not only donor T-cells and host APCs but also TLR ligands and in the presence of high levels of host chimerism depletion of host T-cells CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: A. Ghosh, W. Koestner, M. Hapke, V. Schlaphoff, F. Langer, R. Baumann, C. Koenecke, M. Cornberg, K. Welte, B. R. Blazar, et al. Donor T cells primed on leukemia lysate-pulsed recipient APCs mediate strong graft-versus-leukemia effects across MHC barriers in full chimeras Blood, April 30, 2009; 113(18): 4440 - 4448. [Abstract] [Full Text] [PDF]

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