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Blood, 1 May 2006, Vol. 107, No. 9, pp. 3430-3435. Prepublished online as a Blood First Edition Paper on December 27, 2005; DOI 10.1182/blood-2005-10-4299. This Article Full Text (PDF) All Versions of this Article: 2005-10-4299v1 107/9/3430    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 Morris, E. S Articles by Hill, G. R Search for Related Content PubMed PubMed Citation Articles by Morris, E. S Articles by Hill, G. R Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted October 31, 2005 Accepted December 18, 2005 Stem cell mobilization with G-CSF analogs: A rational approach to separate GVHD and GVL? Edward S Morris, Kelli P MacDonald, and Geoffrey R Hill* Queensland Institute of Medical Research, Brisbane, QLD, Australia * Corresponding author; email: geoffrey.hill{at}qimr.edu.au. The separation of GVHD and GVL remains the "holy grail" of allogeneic stem cell transplantation, and improvements are urgently needed to allow more effective therapy of malignant disease. The use of G-CSF mobilized peripheral blood as a clinical stem cell source is associated with enhanced GVL effects, without amplification of significant acute GVHD. Preclinical studies have demonstrated that G-CSF modulates donor T cell function prior to transplantation, promoting Th2 differentiation and regulatory T cell function. In addition, the expansion of immature APC and plasmacytoid DC favours the maintenance of this pattern of T cell differentiation after transplantation. Although these patterns of T cell differentiation attenuate acute GVHD, they do not impact on the cytolytic pathways of the CD8+ T cell that are critical for effective GVL. Recently, it has been demonstrated that modification of G-CSF, either by pegylation of the native cytokine or conjugation to Flt-3L, results in the expansion and activation of donor iNKT cells, which significantly augment CD8+ T cell-mediated cytotoxicity and GVL effects after transplant. Since these cytokines also enhance the expansion of regulatory T cells and APC, they further separate GVHD and GVL, offering potential clinical advantages for the transplant recipient. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: R. D. Kuns, E. S. Morris, K. P. A. MacDonald, K. A. Markey, H. M. Morris, N. C. Raffelt, T. Banovic, A. L. J. Don, V. Rowe, A. C. Burman, et al. Invariant natural killer T cell-natural killer cell interactions dictate transplantation outcome after {alpha}-galactosylceramide administration Blood, June 4, 2009; 113(23): 5999 - 6010. [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] S. Maury, C. Cordonnier, M. Kuentz, D. Klatzmann, and J. L. Cohen Searching for factors to improve the antileukemic effect of donor lymphocyte infusion Blood, May 15, 2008; 111(10): 5256 - 5256. [Full Text] [PDF] I. Bruns, U. Steidl, J. C. Fischer, A. Czibere, G. Kobbe, S. Raschke, R. Singh, R. Fenk, M. Rosskopf, S. Pechtel, et al. Pegylated granulocyte colony-stimulating factor mobilizes CD34+ cells with different stem and progenitor subsets and distinct functional properties in comparison with unconjugated granulocyte colony-stimulating factor Haematologica, March 1, 2008; 93(3): 347 - 355. [Abstract] [Full Text] [PDF] S. H. C. Baumeister, K. Holig, M. Bornhauser, M. Meurer, E. P. Rieber, and K. Schakel G-CSF mobilizes slanDCs (6-sulfo LacNAc+ dendritic cells) with a high proinflammatory capacity Blood, October 15, 2007; 110(8): 3078 - 3081. [Abstract] [Full Text] [PDF] A. C. Burman, T. Banovic, R. D. Kuns, A. D. Clouston, A. C. Stanley, E. S. Morris, V. Rowe, H. Bofinger, R. Skoczylas, N. Raffelt, et al. IFN{gamma} differentially controls the development of idiopathic pneumonia syndrome and GVHD of the gastrointestinal tract Blood, August 1, 2007; 110(3): 1064 - 1072. [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] 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]

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