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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.
Submitted August 11, 2005
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 * 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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