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Blood, 1 April 2006, Vol. 107, No. 7, pp. 2993-3001. Prepublished online as a Blood First Edition Paper on December 13, 2005; DOI 10.1182/blood-2005-09-3623. This Article Full Text (PDF) Supplemental Figure All Versions of this Article: 2005-09-3623v1 107/7/2993    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 Zhang, C. Articles by Zeng, D. Search for Related Content PubMed PubMed Citation Articles by Zhang, C. Articles by Zeng, D. Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted September 9, 2005 Accepted December 2, 2005 Donor CD4+ T and B cells in transplants induce chronic graft versus host disease with autoimmune manifestations Chunyan Zhang, Ivan Todorov, Zhifang Zhang, Yinping Liu, Fouad Kandeel, Stephen Forman, Samuel Strober, and Defu Zeng* The Beckman Research Institute, City of Hope National Medical Center, Duarte, CA, USA Stanford University School of Medicine, Stanford, CA, USA * Corresponding author; email: dzeng{at}coh.org. Chronic graft-vs-host disease (GVHD) is a major morbidity and mortality of long-term survivors of allogeneic hematopoietic cell transplantation (HCT). Chronic GVHD can have features of an autoimmune collagen-vascular disease with clinical manifestations similar to autoimmune scleroderma and systemic lupus erythematosus (SLE). However, the pathogenesis of chronic GVHD is poorly understood. It is unclear how autoreactive T and B cells are generated in chronic GVHD recipients. We have recently developed a new chronic GVHD model by transplantation of donor DBA/2 (H-2d) spleen cells into MHC-matched but minor antigen-mismatched sublethally irradiated BALB/c (H-2d) recipients, as well as athymic BALB/c nu/nu and adult thymectomized BALB/c recipients. Both euthymic and athymic BALB/c recipients developed high-levels of serum IgG autoantibodies, sclerodermatous skin damage and glomerulonephritis. Disease induction required both donor CD25-CD4+ T and B cells in transplants. In contrast, donor CD25+CD4+ T regulatory (Treg) cells prevented the disease induction. These results indicate that host thymus is not required for induction of chronic GVHD, and that quiescent autoreactive T and B cells in transplants from non-autoimmune donors may be activated and expanded to cause chronic GVHD with autoimmune manifestations in allogeneic recipients, and donor Treg cells can suppress this process. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Of mice and men Judith A. Shizuru Blood 2006 107: 2589-2590. [Full Text] [PDF] This article has been cited by other articles: H. E. Kohrt, B. B. Turnbull, K. Heydari, J. A. Shizuru, G. G. Laport, D. B. Miklos, L. J. Johnston, S. Arai, W.-K. Weng, R. T. Hoppe, et al. TLI and ATG conditioning with low risk of graft-versus-host disease retains antitumor reactions after allogeneic hematopoietic cell transplantation from related and unrelated donors Blood, July 30, 2009; 114(5): 1099 - 1109. [Abstract] [Full Text] [PDF] K. Matthews, Z. Lim, B. Afzali, L. Pearce, A. Abdallah, S. Kordasti, A. Pagliuca, G. Lombardi, J. A. Madrigal, G. J. Mufti, et al. Imbalance of effector and regulatory CD4 T cells is associated with graft-versus-host disease after hematopoietic stem cell transplantation using a reduced intensity conditioning regimen and alemtuzumab Haematologica, July 1, 2009; 94(7): 956 - 966. [Abstract] [Full Text] [PDF] S. Sarantopoulos, K. E. Stevenson, H. T. Kim, C. S. Cutler, N. S. Bhuiya, M. Schowalter, V. T. Ho, E. P. Alyea, J. Koreth, B. R. Blazar, et al. Altered B-cell homeostasis and excess BAFF in human chronic graft-versus-host disease Blood, April 16, 2009; 113(16): 3865 - 3874. [Abstract] [Full Text] [PDF] J. Kim, K. Park, H. J. Kim, J. Kim, H.-A Kim, D. Jung, H. J. Kim, H.-J. Choi, S.-Y. Choi, K. W. Seo, et al. Breaking of CD8+ T Cell Tolerance through In Vivo Ligation of CD40 Results in Inhibition of Chronic Graft-versus-Host Disease and Complete Donor Cell Engraftment J. Immunol., November 15, 2008; 181(10): 7380 - 7389. [Abstract] [Full Text] [PDF] R. Kapur, S. Ebeling, and A. Hagenbeek B-cell involvement in chronic graft-versus-host disease Haematologica, November 1, 2008; 93(11): 1702 - 1711. [Abstract] [Full Text] [PDF] D. Zhao, C. Zhang, T. Yi, C.-L. Lin, I. Todorov, F. Kandeel, S. Forman, and D. Zeng In vivo-activated CD103+CD4+ regulatory T cells ameliorate ongoing chronic graft-versus-host disease Blood, September 1, 2008; 112(5): 2129 - 2138. [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] H. Fujii, G. Cuvelier, K. She, S. Aslanian, H. Shimizu, A. Kariminia, M. Krailo, Z. Chen, R. McMaster, A. Bergman, et al. Biomarkers in newly diagnosed pediatric-extensive chronic graft-versus-host disease: a report from the Children's Oncology Group Blood, March 15, 2008; 111(6): 3276 - 3285. [Abstract] [Full Text] [PDF] S. Sarantopoulos, K. E. Stevenson, H. T. Kim, N. S. Bhuiya, C. S. Cutler, R. J. Soiffer, J. H. Antin, and J. Ritz High Levels of B-Cell Activating Factor in Patients with Active Chronic Graft-Versus-Host Disease Clin. Cancer Res., October 15, 2007; 13(20): 6107 - 6114. [Abstract] [Full Text] [PDF] Y. Zhang, E. Hexner, D. Frank, and S. G. Emerson CD4+ T Cells Generated De Novo from Donor Hemopoietic Stem Cells Mediate the Evolution from Acute to Chronic Graft-versus-Host Disease J. Immunol., September 1, 2007; 179(5): 3305 - 3314. [Abstract] [Full Text] [PDF] J. Kim, H. J. Kim, K. Park, J. Kim, H.-J. Choi, H. Yagita, S. H. Nam, H. R. Cho, and B. Kwon Costimulatory molecule-targeted immunotherapy of cutaneous graft-versus-host disease Blood, July 15, 2007; 110(2): 776 - 782. [Abstract] [Full Text] [PDF] R. Chakraverty and M. Sykes The role of antigen-presenting cells in triggering graft-versus-host disease and graft-versus-leukemia Blood, July 1, 2007; 110(1): 9 - 17. [Abstract] [Full Text] [PDF] Y. Sakoda, D. Hashimoto, S. Asakura, K. Takeuchi, M. Harada, M. Tanimoto, and T. Teshima Donor-derived thymic-dependent T cells cause chronic graft-versus-host disease Blood, February 15, 2007; 109(4): 1756 - 1764. [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] V. Rowe, T. Banovic, K. P. MacDonald, R. Kuns, A. L. Don, E. S. Morris, A. C. Burman, H. M. Bofinger, A. D. Clouston, and G. R. Hill Host B cells produce IL-10 following TBI and attenuate acute GVHD after allogeneic bone marrow transplantation Blood, October 1, 2006; 108(7): 2485 - 2492. [Abstract] [Full Text] [PDF]

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