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Blood, 15 September 2005, Vol. 106, No. 6, pp. 2206-2214. Prepublished online as a Blood First Edition Paper on June 7, 2005; DOI 10.1182/blood-2005-01-0062. This Article Full Text Full Text (PDF) All Versions of this Article: 2005-01-0062v1 106/6/2206    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 Banovic, T. Articles by Hill, G. R. Search for Related Content PubMed PubMed Citation Articles by Banovic, T. Articles by Hill, G. R. Related Collections Immunobiology Transplantation Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  TRANSPLANTATION TGF- in allogeneic stem cell transplantation: friend or foe? Tatjana Banovic, Kelli P. A. MacDonald, Edward S. Morris, Vanessa Rowe, Rachel Kuns, Alistair Don, Jane Kelly, Steve Ledbetter, Andrew D. Clouston, and Geoffrey R. Hill From the Queensland Institute of Medical Research, Queensland, Australia; Department of Stem Cell Transplantation, Royal Brisbane Hospital, Queensland, Australia; Genzyme Corporation, Framingham, MA; and Department of Pathology, University of Queensland, Queensland, Australia. Donor treatment with granulocyte-colony-stimulating factor (G-CSF) attenuates the ability of donor T cells to induce acute graft-versus-host disease (aGVHD) but increases the severity of chronic GVHD (cGVHD). We investigated the role of the regulatory cytokine transforming growth factor (TGF-) in this paradox in well-established murine models of aGVHD and cGVHD wherein recipients undergo transplantation with splenocytes from donors treated with G-CSF. Neutralization of TGF- after stem-cell transplantation (SCT) significantly increased the severity of aGVHD, and the concurrent prevention of interleukin-10 (IL-10) production further exaggerated this effect. Early after SCT, donor T cells were the predominant source of TGF- and were able to attenuate aGVHD in a TGF--dependent fashion. Although the neutralization of TGF- augmented the proliferation and expansion of donor T cells after SCT, it paradoxically impaired cellular cytotoxicity to host antigens and associated graft-versus-leukemia (GVL) effects. In cGVHD, neutralization of TGF- from day 14 after SCT attenuated histologic abnormalities, and CD11b+ mononuclear cells infiltrating sclerodermatous skin produced 50-fold more TGF- than corresponding T cells. Thus, though the production of TGF- by donor T cells early after transplantation attenuates aGVHD and is required for optimal GVL, the production of TGF- late after SCT is preferentially from mononuclear cells and mediates cGVHD. These data have important implications for the timing of therapeutic TGF- neutralization to prevent cGVHD after allogeneic SCT. (Blood. 2005;106:2206-2214) CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: J. Kanter, S. Y. Khan, M. Kelher, L. Gore, and C. C. Silliman Oncogenic and Angiogenic Growth Factors Accumulate during Routine Storage of Apheresis Platelet Concentrates Clin. Cancer Res., June 15, 2008; 14(12): 3942 - 3947. [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] K. P. A. MacDonald, R. D. Kuns, V. Rowe, E. S. Morris, T. Banovic, H. Bofinger, B. O'Sullivan, K. A. Markey, A. L. Don, R. Thomas, et al. Effector and regulatory T-cell function is differentially regulated by RelB within antigen-presenting cells during GVHD Blood, June 1, 2007; 109(11): 5049 - 5057. [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] 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] E. S. Morris, K. P. A. MacDonald, and G. R. Hill Stem cell mobilization with G-CSF analogs: a rational approach to separate GVHD and GVL? Blood, May 1, 2006; 107(9): 3430 - 3435. [Abstract] [Full Text] [PDF] S. Rutella, F. Zavala, S. Danese, H. Kared, and G. Leone Granulocyte Colony-Stimulating Factor: A Novel Mediator of T Cell Tolerance J. Immunol., December 1, 2005; 175(11): 7085 - 7091. [Abstract] [Full Text] [PDF]

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