Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

Immunobiology

G-CSF reduces IFN-γ and IL-4 production by T cells after allogeneic stimulation by indirectly modulating monocyte function

Bone Marrow Transplantation volume 25, pages 1035–1040 (2000)Cite this article

Abstract

Despite a 10-fold increase of T cell dose, the incidence and severity of acute GVHD following allogeneic transplantation of G-CSF-mobilized PBSC is not increased compared to BMT. Experimental murine studies demonstrate that G-CSF polarizes donor T cells toward a type 2 cytokine response. To determine whether G-CSF alters T cell cytokine responses, we investigated the effects of G-CSF administration on T cell proliferative and cytokine responses to alloantigen and Con A in nonadherent PBMC (NAC) and CD3+ T cells obtained from normal individuals before and after G-CSF administration (10 μg/kg × 4 days). Although T cell proliferative and cytokine (IFN-γ and IL-4) responses to alloantigen stimulation and Con A were significantly reduced in post-G-CSF NAC, they were restored by the removal of non-T cells from post-G-CSF NAC. Furthermore, there was less T cell alloreactivity in MLR in the presence of autologous post-G-CSF monocytes than in the presence of pre-G-CSF monocytes. This alteration was not replicated in vitro by culturing PBMC with G-CSF. These results suggest that G-CSF administration suppresses T cell proliferative and cytokine (IFN-γ and IL-4) responses to allogeneic stimulation by indirectly modulating monocyte function. Bone Marrow Transplantation (2000) 25, 1035–1040.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1

Similar content being viewed by others

References

  1. Korbling M, Przepiorka D, Huh YO et al. Allogeneic blood stem cell transplantation for refractory leukemia and lymphoma: potential advantage of blood over marrow allograft Blood 1995 85: 1659–1665

    CAS  PubMed  Google Scholar 

  2. Bensinger WI, Weaver CH, Appelbaum FR et al. Transplantation of allogeneic peripheral blood stem cells mobilized by recombinant human granulocyte colony-stimulating factor Blood 1995 85: 1655–1658

    CAS  PubMed  Google Scholar 

  3. Schmitz N, Dreger P, Suttorp M et al. Primary transplantation of allogeneic peripheral blood progenitor cells mobilized by filgrastim (granulocyte colony-stimulating factor) Blood 1995 85: 1666–1672

    CAS  PubMed  Google Scholar 

  4. Teshima T, Harada M . Mobilization of peripheral blood progenitor cells for allogeneic transplantation Cytok Cell Mol Ther 1997 3: 101–114

    CAS  Google Scholar 

  5. Bensinger WI, Clift R, Martin P et al. Allogeneic peripheral blood stem cell transplantation in patients with advanced hematologic malignancies: a retrospective comparison with marrow transplantation Blood 1996 88: 2794–2800

    CAS  PubMed  Google Scholar 

  6. Ottinger HD, Beelen DW, Scheulen B et al. Improved immune reconstitution after allotransplantation of peripheral blood stem cells instead of bone marrow Blood 1996 88: 2775–2779

    CAS  PubMed  Google Scholar 

  7. Pavletic ZS, Bishop MR, Tarantolo SR et al. Hematopoietic recovery after allogeneic blood stem-cell transplantation compared with bone marrow transplantation in patients with hematologic malignancies J Clin Oncol 1997 15: 1608–1616

    Article  CAS  Google Scholar 

  8. Maeda Y, Teshima T, Yamada M et al. Monitoring of human herpesviruses after allogeneic peripheral blood stem cell transplantation and bone marrow transplantation Br J Haematol 1999 105: 295–302

    Article  CAS  Google Scholar 

  9. Pan L, Delmonte J Jr, Jalonen CK, Ferrara JLM . 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 Blood 1995 86: 4422–4429

    CAS  PubMed  Google Scholar 

  10. Zeng D, Dejbakhsh-Jones S, Strober S . Granulocyte colony-stimulating factor reduces the capacity of blood mononuclear cells to induce graft-versus-host disease: impact on blood progenitor cell transplantation Blood 1997 90: 453–463

    CAS  PubMed  Google Scholar 

  11. Pan L, Teshima T, Hill GR et al. 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 1999 93: 4071–4078

    CAS  PubMed  Google Scholar 

  12. Fowler DH, Kurasawa K, Smith R et al. Donor CD4-enriched cells of Th2 cytokine phenotype regulate graft-versus-host-disease without impairing allogeneic engraftment in sublethally irradiated mice Blood 1994 84: 3540–3549

    CAS  PubMed  Google Scholar 

  13. Kusnierz-Glaz CR, Still BJ, Amano M et al. Granulocyte colony-stimulating factor-induced comobilization of CD4−CD8− T cells and hematopoietic progenitor cells (CD34+) in the blood of normal donors Blood 1997 89: 2586–2595

    CAS  PubMed  Google Scholar 

  14. Rutella S, Rumi C, Monthaje B et al. Serum of healthy donors receiving granulocyte colony-stimulating factor induces T cell unresponsiveness Exp Hematol 1998 26: 1024–1033

    CAS  PubMed  Google Scholar 

  15. Mielcarek M, Martin PJ, Torok-Storb B . Suppression of alloantigen-induced T cell proliferation by CD14+ cells derived from granulocyte colony-stimulating factor-mobilized peripheral blood mononuclear cells Blood 1997 89: 1629–1634

    CAS  PubMed  Google Scholar 

  16. Ageitos AG, Varney ML, Bierman PJ et al. Comparison of monocyte-dependent T cell inhibitory activity in GM-CSF vs G-CSF mobilized PSC products Bone Marrow Transplant 1999 23: 63–69

    Article  CAS  Google Scholar 

  17. Rondelli D, Raspadori D, Anasetti C et al. Alloantigen presenting capacity, T cell alloreactivity and NK function of G-CSF-mobilized peripheral blood cells Bone Marrow Transplant 1998 22: 631–637

    Article  CAS  Google Scholar 

  18. Nawa Y, Teshima T, Sunami K et al. Responses of G-CSF-mobilized peripheral blood mononuclear cells to alloantigen stimulation Blood 1997 90: 1716–1718

    CAS  PubMed  Google Scholar 

  19. Sugimori N, Nakao S, Yachie A et al. Administration of G-CSF to normal individuals diminishes L-selectin+ T cells in the peripheral blood that respond better to alloantigen stimulation than L-selectin− T cells Bone Marrow Transplant 1999 23: 119–124

    Article  CAS  Google Scholar 

  20. Mielcarek M, Graf L, Johnson G, Torok-Storb B . Production of interleukin-10 by granulocyte colony-stimulating factor-mobilized blood products: a mechanism for monocyte-mediated suppression of T-cell proliferation Blood 1998 92: 215–222

    CAS  PubMed  Google Scholar 

  21. Tanaka J, Mielcarek M, Torok-Storb B . Impaired induction of the CD28-responsive complex in granulocyte colony-stimulating factor mobilized CD4 T cells Blood 1998 91: 347–352

    CAS  PubMed  Google Scholar 

  22. Yano T, Katayama Y, Sunami K et al. G-CSF-induced mobilization of peripheral blood stem cells for allografting: comparative study of daily single versus divided dose of G-CSF Int J Hematol 1997 66: 169–178

    Article  CAS  Google Scholar 

  23. Ino K, Singh RK, Talmadge JE . Monocytes from mobilized stem cells inhibit T cell function J Leuk Biol 1997 61: 583–591

    Article  CAS  Google Scholar 

  24. Tanaka J, Imamura M, Zhu X et al. Potential benefit of recombinant human granulocyte colony-stimulating factor-mobilized peripheral blood stem cells for allogeneic transplantation Blood 1994 84: 3595–3596

    CAS  PubMed  Google Scholar 

  25. Shenoy S, Mohanakumar T, Todd G et al. Immune reconstitution following allogeneic peripheral blood stem cell transplants Bone Marrow Transplant 1999 23: 335–346

    Article  CAS  Google Scholar 

  26. Singh RK, Ino K, Varney ML et al. Immunoregulatory cytokines in bone marrow and peripheral blood stem cell products Bone Marrow Transplant 1999 23: 53–62

    Article  CAS  Google Scholar 

  27. Varney ML, Ino K, Ageitos AG et al. Expression of IL-10 in isolated CD8+ T cells and monocytes from growth factor-mobilized peripheral blood stem cell products: a mechanism of immune dysfunction J Interfer Cytok Res 1999 19: 351–360

    Article  CAS  Google Scholar 

  28. Boneberg EM, Hareng L, Gantner F et al. Human monocytes express functional receptors for granulocyte colony-stimulating factor that mediate suppression of monokines and interferon-gamma Blood 2000 95: 270–276

    CAS  PubMed  Google Scholar 

  29. Singh RK, Varney ML, Buyukberber S et al. Fas-FasL-mediated CD4+ T-cell apoptosis following stem cell transplantation Cancer Res 1999 59: 3107–3111

    CAS  PubMed  Google Scholar 

  30. van Furth R, Raeburn JA, van Zwet, TL . Characteristics of human mononuclear phagocytes Blood 1979 54: 485–500

    CAS  PubMed  Google Scholar 

  31. Spector WG, Ryan GB . New evidence for the existence of long lived macrophages Nature 1969 221: 860

    Article  CAS  Google Scholar 

  32. Streck J, Gooley T, Siadak M et al. Allogeneic peripheral blood stem cell transplantation may be associated with a high risk of chronic GVHD Blood 1997 90: 4705–4709

    Google Scholar 

Download references

Acknowledgements

We are grateful to Drs Erik J Carson and Raymond J Hutchinson for helpful discussion and thank Kirin-Sankyo, Chugai Pharmaceuticals Co Ltd, and Kyowa Pharmaceuticals Co Ltd for kindly providing G-CSF. This study is supported in part by a grant-in-aid from the Ministry of Health and Welfare, the Ministry of Education, Science and Culture (06454348), and Uehara Memorial Foundation.

Author information

Authors and Affiliations

  1. Second Department of Medicine, Okayama University Medical School, Okayama, Japan

    Y Nawa, T Teshima, K Sunami, Y Hiramatsu, Y Maeda, T Yano, K Shinagawa, F Ishimaru, E Omoto & M Harada

Authors
  1. Y Nawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. T Teshima
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. K Sunami
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Y Hiramatsu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Y Maeda
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. T Yano
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. K Shinagawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. F Ishimaru
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. E Omoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. M Harada
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Nawa, Y., Teshima, T., Sunami, K. et al. G-CSF reduces IFN-γ and IL-4 production by T cells after allogeneic stimulation by indirectly modulating monocyte function. Bone Marrow Transplant 25, 1035–1040 (2000). https://doi.org/10.1038/sj.bmt.1702402

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.bmt.1702402

Keywords

This article is cited by

Search

Advanced search

Quick links