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Blood, 1 March 2005, Vol. 105, No. 5, pp. 2180-2188. Prepublished online as a Blood First Edition Paper on September 16, 2004; DOI 10.1182/blood-2004-06-2411. This Article Full Text (PDF) All Versions of this Article: 2004-06-2411v1 105/5/2180    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 Liang, Y. Articles by Zeng, D. Search for Related Content PubMed PubMed Citation Articles by Liang, Y. Articles by Zeng, D. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted June 28, 2004 Accepted September 5, 2004 Donor CD8+ T cells facilitate induction of chimerism and tolerance without GVHD in autoimmune NOD mice conditioned with anti-CD3 mAb Yaming Liang, Tammy Huang, Chunyan Zhang, Ivan Todorov, Mark Atkinson, Fouad Kandeel, Stephen Forman, and Defu Zeng* Department of Diabetes and Endocrinology, The Beckman Research Institute, City of Hope National Medical Center, Duarte, CA, USA; Department of Hematology and Hematopoietic Cell Transplantation, The Beckman Research Institute, City of Hope National Medical Center, Duarte, CA, USA Department of Diabetes and Endocrinology, The Beckman Research Institute, City of Hope National Medical Center, Duarte, CA, USA Department of Pathology, Immunology and laboratory Medicine, University of Florida College of Medicine, Gainesville, FL, USA Department of Hematology and Hematopoietic Cell Transplantation, The Beckman Research Institute, City of Hope National Medical Center, Duarte, CA, USA * Corresponding author; email: dzeng{at}coh.org. Prevention of autoimmune diabetes and induction of islet transplantation tolerance in NOD mice can be reached by induction of mixed chimerism via bone marrow transplantation (BMT), but this procedure requires total body irradiation (TBI)-conditioning of the recipients. The toxicity of radiation and potential for graft versus host disease (GVHD) prevents its clinical application. Donor CD8+ T cells play a critical role in facilitation of engraftment, but also contribute to induction of GVHD in TBI-conditioned recipients. Here, we showed that high doses of donor CD8+ T cells in combination with bone marrow (BM) cells induced mixed chimerism without GVHD in NOD recipients conditioned with anti-CD3 mAb. The prevention of GVHD in those recipients was associated with low-level production of inflammatory cytokines (i.e. TNF-), high-level production of anti-inflammatory cytokines (i.e. IL-4 and IL-10), and confining of the donor CD8+ T cell expansion to lymphohematopoietic tissues. The chimeric NOD recipients showed donor specific tolerance and reversal of insulitis. These results demonstrate that donor CD8+ T cell-mediated facilitation of engraftment can be separated from GVHD in non-irradiated recipients. This regimen may have potential application in the treatment of autoimmune disorders as well as induction of transplantation tolerance. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: D. Gibbings and A. D. Befus CD4 and CD8: an inside-out coreceptor model for innate immune cells J. Leukoc. Biol., August 1, 2009; 86(2): 251 - 259. [Abstract] [Full Text] [PDF] T. Yi, D. Zhao, C.-L. Lin, C. Zhang, Y. Chen, I. Todorov, T. LeBon, F. Kandeel, S. Forman, and D. Zeng Absence of donor Th17 leads to augmented Th1 differentiation and exacerbated acute graft-versus-host disease Blood, September 1, 2008; 112(5): 2101 - 2110. [Abstract] [Full Text] [PDF] W. F. N. Chan, H. Razavy, B. Luo, A. M. J. Shapiro, and C. C. Anderson Development of Either Split Tolerance or Robust Tolerance along with Humoral Tolerance to Donor and Third-Party Alloantigens in Nonmyeloablative Mixed Chimeras J. Immunol., April 15, 2008; 180(8): 5177 - 5186. [Abstract] [Full Text] [PDF] N. Li, D. Zhao, M. Kirschbaum, C. Zhang, C.-L. Lin, I. Todorov, F. Kandeel, S. Forman, and D. Zeng HDAC inhibitor reduces cytokine storm and facilitates induction of chimerism that reverses lupus in anti-CD3 conditioning regimen PNAS, March 25, 2008; 105(12): 4796 - 4801. [Abstract] [Full Text] [PDF] C. Zhang, I. Todorov, C.-L. Lin, M. Atkinson, F. Kandeel, S. Forman, and D. Zeng Elimination of insulitis and augmentation of islet beta cell regeneration via induction of chimerism in overtly diabetic NOD mice PNAS, February 13, 2007; 104(7): 2337 - 2342. [Abstract] [Full Text] [PDF] C. Zhang, J. Lou, N. Li, I. Todorov, C.-L. Lin, Y.-A. Cao, C. H. Contag, F. Kandeel, S. Forman, and D. Zeng Donor CD8+ T Cells Mediate Graft-versus-Leukemia Activity without Clinical Signs of Graft-versus-Host Disease in Recipients Conditioned with Anti-CD3 Monoclonal Antibody J. Immunol., January 15, 2007; 178(2): 838 - 850. [Abstract] [Full Text] [PDF] D. V. Serreze, M. A. Osborne, Y.-G. Chen, H. D. Chapman, T. Pearson, M. A. Brehm, and D. L. Greiner Partial versus Full Allogeneic Hemopoietic Chimerization Is a Preferential Means to Inhibit Type 1 Diabetes as the Latter Induces Generalized Immunosuppression J. Immunol., November 15, 2006; 177(10): 6675 - 6684. [Abstract] [Full Text] [PDF] A. S. Narang and R. I. Mahato Biological and biomaterial approaches for improved islet transplantation. Pharmacol. Rev., June 1, 2006; 58(2): 194 - 243. [Abstract] [Full Text] [PDF] C. Zhang, I. Todorov, Z. Zhang, Y. Liu, F. Kandeel, S. Forman, S. Strober, and D. Zeng Donor CD4+ T and B cells in transplants induce chronic graft-versus-host disease with autoimmune manifestations Blood, April 1, 2006; 107(7): 2993 - 3001. [Abstract] [Full Text] [PDF]

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