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Blood, 1 September 2008, Vol. 112, No. 5, pp. 2129-2138. Prepublished online as a Blood First Edition Paper on June 12, 2008; DOI 10.1182/blood-2008-02-140277. This Article Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2008-02-140277v1 112/5/2129    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 Zhao, D. Articles by Zeng, D. Search for Related Content PubMed PubMed Citation Articles by Zhao, D. Articles by Zeng, D. Related Collections Related Articles in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted February 27, 2008 Accepted May 13, 2008 In vivo activated CD103+CD4+ regulatory T cells ameliorate ongoing chronic GVHD Dongchang Zhao, Chunyan Zhang, Tangsheng Yi, Chia-Lei Lin, Ivan Todorov, Fouad Kandeel, Stephen Forman, and Defu Zeng* Department of Diabetes/Endocrinology, The Beckman Research Institute, City of Hope National Medical Center, Duarte, CA, United States Division of Hematology/Hematopoietic Cell Transplantation, The Beckman Research Institute, City of Hope National Medical Center, Duarte, CA, United States City of Hope Graduate School of Biological Sciences, The Beckman Research Institute, City of Hope National Medical Center, Duarte, CA, United States * Corresponding author; email: dzeng{at}coh.org. CD103 has been shown to be an excellent marker for identifying in vivo activated FoxP3+CD4+ Treg cells. It is unknown whether re-infusion of in vivo activated donor-type CD103+ Treg cells from recipient can ameliorate ongoing chronic GVHD. Here, we showed that, in a chronic GVHD model of DBA/2 (H-2d) donor to BALB/c (H-2d) recipient, donor-type CD103+ Treg cells from recipients were much more potent than CD25hi natural Treg cells from donor in reversing clinical signs of GVHD and tissue damage. Furthermore, in contrast to CD25hi natural Treg cells, the CD103+ Treg cells expressed high levels of CCR5 but low levels of CD62L and directly migrated to GVHD target tissues. In addition, the CD103+ Treg cells strongly suppressed donor CD4+ T cell proliferation; they also induced apoptosis of in vivo activated CD4+ T and B cells and significantly reduced pathogenic T and B cells in GVHD target tissues. These results indicate that CD103+ Treg cells from chronic GVHD recipients are functional, and re-infusion of the CD103+ Treg cells can shift the balance between Treg cells and pathogenic T cells in chronic GVHD recipients and ameliorate ongoing disease. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Articles in Blood Online: In vivo–activated CD103+ Foxp3+ Tregs: of men and mice Olaf Rötzschke, Giovanna Borsellino, Luca Battistini, Kirsten Falk, and Markus Kleinewietfeld Blood 2009 113: 2119-2120. [Full Text] [PDF] Response: Is CD103 a good surface marker for in vivo–activated effector/memory Treg cells in patients with chronic inflammation? Unknown yet Defu Zeng, Dongchang Zhao, and Ryotaro Nakamura Blood 2009 113: 2120. [Full Text] [PDF] This article has been cited by other articles: A. M. Wolf, K. Eller, R. Zeiser, C. Durr, U. V. Gerlach, M. Sixt, L. Markut, G. Gastl, A. R. Rosenkranz, and D. Wolf The Sphingosine 1-Phosphate Receptor Agonist FTY720 Potently Inhibits Regulatory T Cell Proliferation In Vitro and In Vivo J. Immunol., September 15, 2009; 183(6): 3751 - 3760. [Abstract] [Full Text] [PDF] X. Chen, R. Das, R. Komorowski, A. Beres, M. J. Hessner, M. Mihara, and W. R. Drobyski Blockade of interleukin-6 signaling augments regulatory T-cell reconstitution and attenuates the severity of graft-versus-host disease Blood, July 23, 2009; 114(4): 891 - 900. [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] Y.-C. Lin, L.-Y. Chang, C.-T. Huang, H.-M. Peng, A. Dutta, T.-C. Chen, C.-T. Yeh, and C.-Y. Lin Effector/Memory but Not Naive Regulatory T Cells Are Responsible for the Loss of Concomitant Tumor Immunity J. Immunol., May 15, 2009; 182(10): 6095 - 6104. [Abstract] [Full Text] [PDF] O. Rotzschke, G. Borsellino, L. Battistini, K. Falk, and M. Kleinewietfeld In vivo-activated CD103+ Foxp3+ Tregs: of men and mice Blood, February 26, 2009; 113(9): 2119 - 2120. [Full Text] [PDF] D. Zeng, D. Zhao, and R. Nakamura Response: Is CD103 a good surface marker for in vivo-activated effector/memory Treg cells in patients with chronic inflammation? Unknown yet Blood, February 26, 2009; 113(9): 2120 - 2120. [Full Text] [PDF] N. Li, Y. Chen, W. He, T. Yi, D. Zhao, C. Zhang, C.-L. Lin, I. Todorov, F. Kandeel, S. Forman, et al. Anti-CD3 preconditioning separates GVL from GVHD via modulating host dendritic cell and donor T-cell migration in recipients conditioned with TBI Blood, January 22, 2009; 113(4): 953 - 962. [Abstract] [Full Text] [PDF]

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