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Prepublished online as a Blood First Edition Paper on October 17, 2002; DOI 10.1182/blood-2002-05-1529. This Article Full Text (PDF) All Versions of this Article: 2002-05-1529v1 101/5/2033    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 MacDonald, K. P Articles by Hill, G. R Search for Related Content PubMed PubMed Citation Articles by MacDonald, K. P Articles by Hill, G. R Social Bookmarking                   What's this? Submitted May 24, 2002 Accepted September 27, 2002 Donor Pretreatment with Progenipoietin-1 is Superior to G-CSF in Preventing Graft-versus-Host Disease after Allogeneic Stem Cell Transplantation Kelli P MacDonald, Vanessa Rowe, Cheryl Filippich, Ranjeny Thomas, Andrew D Clouston, Joseph K Welply, Derek N Hart, James L Ferrara, and Geoffrey R Hill* Infectious Diseases and Immunology, The Queensland Institute of Medical Research, Brisbane, QLD, Australia; Mater Medical Research Institute, Brisbane, QLD, Australia Centre for Immunology and Cancer Research, Brisbane, QLD, Australia Department of Pathology, University of Queensland, Brisbane, QLD, Australia Division of Oncology, Pharmacia, St Louis, MO, USA Mater Medical Research Institute, Brisbane, QLD, Australia Department of Internal Medicine and Pediatrics, University of Michigan, Ann Arbor, MI, USA Infectious Diseases and Immunology, The Queensland Institute of Medical Research, Brisbane, QLD, Australia; Mater Medical Research Institute, Brisbane, QLD, Australia; Department of Stem Cell Transplantation, Royal Brisbane Hospital, Brisbane, QLD, Australia * Corresponding author; email: geoffH{at}qimr.edu.au. The G-CSF and FLT-3L receptor agonist Progenipoietin-1 (ProGP-1) has potent effects on dendritic cell (DC) expansion and may be an alternative to G-CSF for the mobilization of stem cells for allogeneic stem cell transplantation (SCT). We studied the ability of stem cell grafts mobilized with this agent to induce graft-versus-host disease (GVHD) to minor and major histocompatibility antigens in the well described B6 B6D2F1 SCT model. ProGP-1, G-CSF or control diluent was administered to donor B6 mice. ProGP-1 expanded all cell lineages in the spleen and unseparated splenocytes from these animals produced large amounts of IL-10 and TGFß while the expression of T cell adhesion molecules was diminished. Transplant survival was 0%, 50% and 90% in recipients of control, G-CSF and ProGP-1 treated allogeneic donor splenocytes respectively (P<0.0001). Donor pretreatment with ProGP-1 allowed a four-fold escalation in T cell dose over that possible with G-CSF. Donor CD4 T cells from allogeneic SCT recipients of ProGP-1 splenocytes demonstrated an anergic response to host antigen and cytokine production (IFN, IL-4 and IL-10) was also reduced while CD8 T cell cytotoxicity to host antigens remained intact. Neither CD11chi DC nor CD11cdim/B220hi DC from ProGP-1 treated animals conferred protection from GVHD when added to control spleen. Conversely, when equal numbers of purified T cells from control, G-CSF or ProGP-1 treated allogeneic donors were added to allogeneic T-cell depleted control spleen, survival at day 60 was 0%, 15% and 90% respectively (P<0.0001). The improved survival in recipients of ProGP-1 T cells was associated with reductions in systemic TNF generation and GVHD of the GI tract. We conclude that donor pretreatment with ProGP-1 is superior to G-CSF for the prevention of GVHD after allogeneic SCT, primarily due to incremental affects on T cell phenotype and function. 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