Pretransplant CSF-1 therapy expands recipient macrophages and ameliorates GVHD after allogeneic hematopoietic cell transplantation

Daigo Hashimoto, Andrew Chow, Melanie Greter, Yvonne Saenger, Wing Hong Kwan, Marylene Leboeuf, Florent Ginhoux, Jordi C. Ochando, Yuya Kunisaki, Nico van Rooijen, Chen Liu, Takanori Teshima, Peter S. Heeger, E. Richard Stanley, Paul S. Frenette, Miriam Merad

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87 Scopus citations

Abstract

Acute graft-versus-host disease (GVHD) results from the attack of host tissues by donor allogeneic T cells and is the most serious limitation of allogeneic hematopoietic cell transplantation (allo-HCT). Host antigen-presenting cells are thought to control the priming of alloreactive T cells and the induction of acute GVHD after allo-HCT. However, whereas the role of host DC in GVHD has been established, the contribution of host macrophages to GVHD has not been clearly addressed. We show that, in contrast to DC, reducing of the host macrophage pool in recipient mice increased donor T cell expansion and aggravated GVHD mortality after allo-HCT. We also show that host macrophages that persist after allo-HCT engulf donor allogeneic T cells and inhibit their proliferation. Conversely, administration of the cytokine CSF-1 before transplant expanded the host macrophage pool, reduced donor T cell expansion, and improved GVHD morbidity and mortality after allo-HCT. This study establishes the unexpected key role of host macrophages in inhibiting GVHD and identifies CSF-1 as a potential prophylactic therapy to limit acute GVHD after allo-HCT in the clinic.

Original languageEnglish (US)
Pages (from-to)1069-1082
Number of pages14
JournalJournal of Experimental Medicine
Volume208
Issue number5
DOIs
StatePublished - May 1 2011

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Hashimoto, D., Chow, A., Greter, M., Saenger, Y., Kwan, W. H., Leboeuf, M., Ginhoux, F., Ochando, J. C., Kunisaki, Y., van Rooijen, N., Liu, C., Teshima, T., Heeger, P. S., Stanley, E. R., Frenette, P. S., & Merad, M. (2011). Pretransplant CSF-1 therapy expands recipient macrophages and ameliorates GVHD after allogeneic hematopoietic cell transplantation. Journal of Experimental Medicine, 208(5), 1069-1082. https://doi.org/10.1084/jem.20101709