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Blood, 1 March 2006, Vol. 107, No. 5, pp. 2192-2199.
Prepublished online as a Blood First Edition Paper on October 25, 2005; DOI 10.1182/blood-2005-08-3239.


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Submitted August 11, 2005
Accepted October 14, 2005

G-CSF treated granulocytes inhibit acute graft versus host disease

Zilton F Vasconcelos, Bruna M dos Santos, Julia Farache, Tereza S Palmeira, Romulo B Areal, Jose M Cunha, Marcello A Barcinski, and Adriana Bonomo*

Divisao de Medicina Experimental, Coordenacao de Pesquisa, Instituto Nacional de Cancer, Rio de Janeiro, Brazil; Banco de Sangue de Cordao Umbilical e Placentario, Centro de Transplante de Medula Ossea, Instituto Nacional de Cancer, Rio de Janeiro, Brazil; Departamento de Imunologia, Instituto de Microbiologia Prof. Paulo de Goes, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
Divisao de Medicina Experimental, Coordenacao de Pesquisa, Instituto Nacional de Cancer, Rio de Janeiro, Brazil; Departamento de Imunologia, Instituto de Microbiologia Prof. Paulo de Goes, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
Divisao de Medicina Experimental, Coordenacao de Pesquisa, Instituto Nacional de Cancer, Rio de Janeiro, Brazil
Divisao de Medicina Experimental, Coordenacao de Pesquisa, Instituto Nacional de Cancer, Rio de Janeiro, Brazil; Faculdade de Ciencias Biologicas, Universidade Federal de Vicosa, Vicosa, Minas Gerais, Brazil
Instituto de Pediatria e Puericultura Martagao Gesteira, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
Divisao de Medicina Experimental, Coordenacao de Pesquisa, Instituto Nacional de Cancer, Rio de Janeiro, Brazil; Departamento de Parasitologia, Instituto de Ciencias Biomedicas, Universidade de Sao Paulo, Sao Paulo, Brazil

* Corresponding author; email: abonomo{at}inca.gov.br.

It has been shown that in vivo and in vitro treatment with G-CSF induces the generation of low-density granulocytes (LDGs) which co-purify with PBMCs and inhibit gamma-IFN production by human T cells. These results prompted us to postulate an immunomodulatory role for LDGs in aGVHD. Here it is shown that in the mouse experimental model, in vivo and in vitro G-CSF treatment generates LDGs capable of inhibiting 80% of T cell gamma-IFN production. In order to assess the role of these LDGs in aGVHD, lethally irradiated (C57BL/6 x BALB/c)F1 hosts were reconstituted with T-cell-depleted bone-marrow cells plus nylon-wool purified spleen cells from G-CSF treated (G-NWS) or non-treated (NWS) C57BL/6 donors. Recipients of G-NWS showed 75% survival rate in contrast to 25% in the NWS recipients. The protective effect is completely abolished, with 100% mortality being observed, if donor-cell infusion is treated with anti-Gr1. Moreover if LDGs are infused with NWS, a full protection of aGVHD is observed, with no signs of disease assessed by mortality rate, weight loss and histopathology of target organs. These results uncover the unexpected immuno-suppressive capacity of G-CSF based on the generation of LDGs which opens the perspective of using these cells as inhibitors of aGVHD.


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