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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 (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 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 Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted January 7, 2005 Accepted May 5, 2005 TGF in allogeneic stem cell transplantation: Friend or foe? Tatjana Banovic, Kelli P MacDonald, Edward S Morris, Vanessa Rowe, Rachel Kuns, Alistair Don, Jane Kelly, Steven Ledbetter, Andrew D Clouston, and Geoffrey R Hill* The Queensland Institute of Medical Research, Brisbane, QLD, Australia The Queensland Institute of Medical Research, Brisbane, QLD, Australia; Department of Stem Cell Transplantation, Royal Brisbane Hospital, Brisbane, QLD, Australia Genzyme Corporation, Framingham, MA, USA Department of Pathology, University of Queensland, Brisbane, QLD, Australia * Corresponding author; email: Geoff.Hill{at}qimr.edu.ai. Donor treatment with G-CSF attenuates the ability of donor T cells to induce acute GVHD (aGVHD) but increases the severity of chronic GVHD (cGVHD). We investigated the role of the regulatory cytokine TGF in this paradox in well established murine models of acute and chronic GVHD where recipients are transplanted with splenocytes from donors treated with G-CSF. Neutralization of TGF after stem cell transplantation (SCT) significantly increased aGVHD and the concurrent prevention of IL-10 production further exaggerated this effect. Early following SCT, donor T cells were the predominant source of TGF and were able to attenuate aGVHD in a TGF-dependant fashion. Whilst 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 histopathology and CD11b+ mononuclear cells infiltrating sclerodermatous skin produced 50-fold more TGF than corresponding T cells. Thus, while 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. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: N. Matsuno, A. Wake, N. Uchida, K. Ishiwata, H. Araoka, S. Takagi, M. Tsuji, H. Yamamoto, D. Kato, Y. Matsuhashi, et al. Impact of HLA disparity in the graft-versus-host direction on engraftment in adult patients receiving reduced-intensity cord blood transplantation Blood, August 20, 2009; 114(8): 1689 - 1695. [Abstract] [Full Text] [PDF] T. Banovic, K. A. Markey, R. D. Kuns, S. D. Olver, N. C. Raffelt, A. L. Don, M. A. Degli-Esposti, C. R. Engwerda, K. P. A. MacDonald, and G. R. Hill Graft-versus-Host Disease Prevents the Maturation of Plasmacytoid Dendritic Cells J. Immunol., January 15, 2009; 182(2): 912 - 920. [Abstract] [Full Text] [PDF] J. Kanter, S. Y. Khan, M. Kelher, L. Gore, and C. C. 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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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