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

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...

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Detalles Bibliográficos
Autores: Hashimoto, Daigo, Chow, Andrew, Greter, Melanie, Saenger, Yvonne, Kwan, Wing-Hong, Leboeuf, Marylene, Ginhoux, Florent, Ochando, Jordi, Kunisaki, Yuya, van Rooijen, Nico, Liu, Chen, Teshima, Takanori, Heeger, Peter S, Stanley, E Richard, Frenette, Paul S, Merad, Miriam
Tipo de recurso: artículo
Fecha de publicación:2011
País:España
Institución:Instituto de Salud Carlos III (ISCIII)
Repositorio:Repisalud
Idioma:inglés
OAI Identifier:oai:repisalud.isciii.es:20.500.12105/8545
Acceso en línea:http://hdl.handle.net/20.500.12105/8545
Access Level:acceso abierto
Palabra clave:Animals
Antigen-Presenting Cells
Female
Graft vs Host Disease
Macrophage Colony-Stimulating Factor
Macrophages
Male
Mice
Mice, Inbred BALB C
Mice, Knockout
T-Lymphocytes
Transplantation, Homologous
Hematopoietic Stem Cell Transplantation
Descripción
Sumario: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.

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