Donor pretreatment with progenipoietin-1 is superior to granulocyte colony-stimulating factor in preventing graft-versus-host disease after allogeneic stem cell transplantation

MacDonald, Kelli P. A., Rowe, Vanessa, Filippich, Cheryl, Thomas, Ranjeny, Clouston, Andrew D., Welply, Joseph K., Hart, Derek N. J., Ferrara, James L. M. and Hill, Geoffrey R. (2003) Donor pretreatment with progenipoietin-1 is superior to granulocyte colony-stimulating factor in preventing graft-versus-host disease after allogeneic stem cell transplantation. Blood, 101 5: 2033-2042. doi:10.1182/blood-2002-05-1529


Author MacDonald, Kelli P. A.
Rowe, Vanessa
Filippich, Cheryl
Thomas, Ranjeny
Clouston, Andrew D.
Welply, Joseph K.
Hart, Derek N. J.
Ferrara, James L. M.
Hill, Geoffrey R.
Title Donor pretreatment with progenipoietin-1 is superior to granulocyte colony-stimulating factor in preventing graft-versus-host disease after allogeneic stem cell transplantation
Journal name Blood   Check publisher's open access policy
ISSN 0006-4971
1528-0020
Publication date 2003-03
Sub-type Article (original research)
DOI 10.1182/blood-2002-05-1529
Volume 101
Issue 5
Start page 2033
End page 2042
Total pages 10
Place of publication Washington, DC, United States
Publisher American Society of Hematology
Collection year 2003
Language eng
Subject 320202 Cellular Immunology
730102 Immune system and allergy
110704 Cellular Immunology
1107 Immunology
Abstract The granulocyte colony-stimulating factor (G-CSF) and Fit-3 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-CSIF, 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 interleukin 10 (IL-10) and transforming growth factor beta (TGFbeta) whereas the expression of T-cell adhesion molecules was diminished. Transplantation survival was 0%, 50%, and 90% in recipients of control-, G-CSF-, and ProGP-1-treated allogeneic donor splenocytes, respectively (P < .0001). Donor pretreatment with ProGP-1 allowed a 4-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 (interferon gamma [IFNγ], IL-4, and IL-10) was also reduced while CD8 T-cell cytotoxicity to host antigens remained intact. Neither CD11c(hi) DCs nor CD11c(dim)/B220(hi) DCs 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 < .0001). The improved survival in recipients of ProGP-1 T cells was associated with reductions in systemic tumor necrosis factor alpha generation and GVHD of the gastrointestinal tract. We conclude that donor pretreatment with ProGP-1 is superior to G-CSIF for the prevention of GVHD after allogeneic SCT, primarily due to incremental affects on T-cell phenotype and function
Keyword Bone-marrow transplantation
Liver Tyrosine Kinase-3
Necrosis-factor-alpha
Dendritic cells
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

 
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Created: Wed, 15 Aug 2007, 02:43:55 EST