G-CSF-treated uanulocytes inhibit acute graft-versus-host disease

It has been shown that in vivo and in vitro treatment with G-CSF induces the generation of low-density granulocytes (LUGS), which copurify with PBMCs and inhibit IFN-gamma 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 it 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-gamma production. 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 -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 ob-served, 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.