|
|
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.
Previous Article | Table of Contents | Next Article 
TRANSPLANTATION
G-CSFtreated granulocytes inhibit acute graft-versus-host disease
Zilton F. M. Vasconcelos,
Bruna M. dos Santos,
Julia Farache,
Tereza S. S. Palmeira,
Rômulo B. Areal,
José Marcos T. Cunha,
Marcello A. Barcinski, and
Adriana Bonomo
From the Divisão de Medicina Experimental, Coordenação de Pesquisa, Instituto Nacional de Câncer; Banco de Sangue de Cordão Umbilical e Placentário, Centro de Transplante de Medula Óssea, Instituto Nacional de Câncer, Rio de Janeiro; Departamento de Parasitologia, Instituto de Ciências Biomédicas, Universidade de São Paulo; Departamento de Imunologia, Instituto de Microbiologia Prof. Paulo de Góes, Universidade Federal do Rio de Janeiro; Faculdade de Ciências Biológicas, Universidade Federal de Viçosa, Minas Gerais; and Instituto de Pediatria e Puericultura Martagão Gesteira, Universidade Federal do Rio de Janeiro, Brazil.
It has been shown that in vivo and in vitro treatment with G-CSF induces the generation of low-density granulocytes (LDGs), which copurify with PBMCs and inhibit IFN- production by human T cells. These results prompted us to postulate an immunomodulatory role for LDGs in acute graft-versus-host disease (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 IFN- production. To assess the role of these LDGs in aGVHD, lethally irradiated (C57BL/6 x BALB/c) F1 hosts were reconstituted with T celldepleted bone marrow cells plus nylon woolpurified spleen cells from G-CSFtreated (G-NWS) or nontreated (NWS) C57BL/6 donors. Recipients of G-NWS had a 75% survival rate in contrast to a rate of 25% in the NWS recipients. The protective effect was completely abolished, and the mortality rate was 100% if donor-cell infusion was treated with anti-Gr1. Moreover, if LDGs were infused with NWS, full protection of aGVHD was observed, and no signs of disease were evidenced by mortality rate, weight loss, or histopathology of target organs. These results revealed the unexpected immunosuppressive capacity of G-CSF based on the generation of LDGs, leading to the possibility of using these cells as inhibitors of aGVHD.

CiteULike Connotea Del.icio.us Digg Reddit Technorati What's this?
This article has been cited by other articles:

|
 |

|
 |
 
K. Movahedi, M. Guilliams, J. Van den Bossche, R. Van den Bergh, C. Gysemans, A. Beschin, P. De Baetselier, and J. A. Van Ginderachter
Identification of discrete tumor-induced myeloid-derived suppressor cell subpopulations with distinct T cell-suppressive activity
Blood,
April 15, 2008;
111(8):
4233 - 4244.
[Abstract]
[Full Text]
[PDF]
|
 |
|
|
|