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Pretreatment of donor mice with granulocyte colony-stimulating factor
polarizes donor T lymphocytes toward type-2 cytokine production and reduces
severity of experimental graft-versus-host disease
L Pan, J Delmonte , CK Jalonen and JL Ferrara
Division of Pediatric Oncology, Dana Farber Cancer Institute, Boston, MA
02115, USA.
The incidence and severity of acute graft-versus-host disease (GVHD) after
allogeneic transplantation using peripheral blood progenitor cells
mobilized by granulocyte colony-stimulating factor (G-CSF) appear to be no
worse than those after bone marrow transplantation, despite the presence of
large numbers of T cells in the donor infusion. Experimental studies have
shown that type-1 T cells (secreting interleukin-2 [IL-2] and
interferon-gamma) mediate acute GVHD, whereas type-2 T cells (secreting
IL-4 and IL-10) can prevent acute GVHD. We tested the hypothesis that G-CSF
modulates T-cell function toward a type-2 response and thus reduces the
severity of acute GVHD. B6 mice were injected with G-CSF or diluent for 4
days, and their splenic T cells were stimulated in vitro with alloantigen
or mitogen in the absence of G-CSF. T cells from G-CSF-treated mice showed
a significant increase in IL-4 production, with a simultaneous decrease in
IL-2 and interferon-gamma production in response to both stimuli. We also
examined the effect of G-CSF pretreatment of donors in a GVHD model (B6-
->B6D2F1). Survival was significantly improved in recipients of G-CSF-
treated donors. Concanavalin-A-induced cytokine production at day 13 after
transplantation also showed an increase in IL-4 along with a decrease in
IL-2 and IFN-gamma production by splenocytes from recipients of
G-CSF-treated bone marrow and T cells. These data show that pretreatment of
donors with G-CSF polarizes donor T cells toward the production of type-2
cytokines, which is associated with reduced type-1 cytokine production and
reduced severity of acute GVHD.
Volume 86,
Issue 12,
pp. 4422-4429,
12/15/1995
Copyright © 1995 by The American Society of Hematology
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F. R. Appelbaum
Choosing the Source of Stem Cells for Allogeneic Transplantation: No Longer a Peripheral Issue
Blood,
July 15, 1999;
94(2):
381 - 383.
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M. Engelhardt, H. Bertz, M. Afting, C. F. Waller, and J. Finke
High- Versus Standard-Dose Filgrastim (rhG-CSF) for Mobilization of Peripheral-Blood Progenitor Cells From Allogeneic Donors and CD34+ Immunoselection
J. Clin. Oncol.,
July 1, 1999;
17(7):
2160 - 2160.
[Abstract]
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R. K. Singh, M. L. Varney, S. Buyukberber, K. Ino, A. G. Ageitos, E. Reed, S. Tarantolo, and J. E. Talmadge
Fas-FasL-mediated CD4+ T-Cell Apoptosis following Stem Cell Transplantation
Cancer Res.,
July 1, 1999;
59(13):
3107 - 3111.
[Abstract]
[Full Text]
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L. Pan, T. Teshima, G. R. Hill, D. Bungard, Y. S. Brinson, V. S. Reddy, K. R. Cooke, and J. L.M. Ferrara
Granulocyte Colony-Stimulating Factor-Mobilized Allogeneic Stem Cell Transplantation Maintains Graft-Versus-Leukemia Effects Through a Perforin-Dependent Pathway While Preventing Graft-Versus-Host Disease
Blood,
June 15, 1999;
93(12):
4071 - 4078.
[Abstract]
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M.L.U. del Rosario, J. R. Zucali, and K.J. Kao
Prevention of Graft-Versus-Host Disease by Induction of Immune Tolerance With Ultraviolet B-Irradiated Leukocytes in H-2 Disparate Bone Marrow Donor
Blood,
May 15, 1999;
93(10):
3558 - 3564.
[Abstract]
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R. A. Brown, D. Adkins, H. Khoury, R. Vij, L. T. Goodnough, S. Shenoy, and J. F. DiPersio
Long-Term Follow-Up of High-Risk Allogeneic Peripheral-Blood Stem-Cell Transplant Recipients: Graft-Versus-Host Disease and Transplant-Related Mortality
J. Clin. Oncol.,
March 1, 1999;
17(3):
806 - 806.
[Abstract]
[Full Text]
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M. Weiss, L. L. Moldawer, and E. M. Schneider
Granulocyte Colony-Stimulating Factor to Prevent the Progression of Systemic Nonresponsiveness in Systemic Inflammatory Response Syndrome and Sepsis
Blood,
January 15, 1999;
93(2):
425 - 439.
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M. Mielcarek, L. Graf, G. Johnson, and B. Torok-Storb
Production of Interleukin-10 by Granulocyte Colony-Stimulating Factor-Mobilized Blood Products: A Mechanism for Monocyte-Mediated Suppression of T-Cell Proliferation
Blood,
July 1, 1998;
92(1):
215 - 222.
[Abstract]
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B. R. Blazar, P. A. Taylor, A. Panoskaltsis-Mortari, and D. A. Vallera
Rapamycin Inhibits the Generation of Graft-Versus-Host Disease- and Graft-Versus-Leukemia-Causing T Cells by Interfering with the Production of Th1 or Th1 Cytotoxic Cytokines
J. Immunol.,
June 1, 1998;
160(11):
5355 - 5365.
[Abstract]
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J. Storek, T. Gooley, M. Siadak, W. I. Bensinger, D. G. Maloney, T. R. Chauncey, M. Flowers, K. M. Sullivan, R. P. Witherspoon, S. D. Rowley, et al.
Allogeneic Peripheral Blood Stem Cell Transplantation May Be Associated With a High Risk of Chronic Graft-Versus-Host Disease
Blood,
December 15, 1997;
90(12):
4705 - 4709.
[Abstract]
[Full Text]
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B. Glass, L. Uharek, M. Zeis, P. Dreger, H. Loffler, J. Steinmann, and N. Schmitz
Allogeneic Peripheral Blood Progenitor Cell Transplantation in a Murine Model: Evidence for an Improved Graft-Versus-Leukemia Effect
Blood,
August 15, 1997;
90(4):
1694 - 1700.
[Abstract]
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Y. Nawa, T. Teshima, K. Sunami, Y. Hiramatsu, T. Yano, K. Shinagawa, E. Omoto, and M. Harada
Responses of Granulocyte Colony-Stimulating Factor-Mobilized Peripheral Blood Mononuclear Cells to Alloantigen Stimulation
Blood,
August 15, 1997;
90(4):
1716 - 1718.
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D. Zeng, S. Dejbakhsh-Jones, and S. Strober
Granulocyte Colony-Stimulating Factor Reduces the Capacity of Blood Mononuclear Cells to Induce Graft-Versus-Host Disease: Impact on Blood Progenitor Cell Transplantation
Blood,
July 1, 1997;
90(1):
453 - 463.
[Abstract]
[Full Text]
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C. R. Kusnierz-Glaz, B. J. Still, M. Amano, J. D. Zukor, R. S. Negrin, K. G. Blume, and S. Strober
Granulocyte Colony-Stimulating Factor-Induced Comobilization of CD4-CD8- T Cells and Hematopoietic Progenitor Cells (CD34+) in the Blood of Normal Donors
Blood,
April 1, 1997;
89(7):
2586 - 2595.
[Abstract]
[Full Text]
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M. Mielcarek, P. J. Martin, and B. Torok-Storb
Suppression of Alloantigen-Induced T-Cell Proliferation by CD14+ Cells Derived From Granulocyte Colony-Stimulating Factor-Mobilized Peripheral Blood Mononuclear Cells
Blood,
March 1, 1997;
89(5):
1629 - 1634.
[Abstract]
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K. Iizuka, H. Kaneko, T. Yamada, H. Kimura, Y. Kokai, and J. Fujimoto
Host F1 Mice Pretreated With Granulocyte Colony-Stimulating Factor Accept Parental Bone Marrow Grafts in Hybrid Resistance System
Blood,
February 15, 1997;
89(4):
1446 - 1451.
[Abstract]
[Full Text]
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