It has been shown that in vivo and in vitrotreatment with G-CSF induces the generation of low-density granulocytes (LDGs), which copurify with PBMCs and inhibit IFN-g production by humanT cells. These results prompted us to postulate an immunomodulatory role for LDGs in acute graftversus-host disease (aGVHD). Here it is shown that in the mouseexperimental model, in vivo and in vitroG-CSFtreatment generates LDGs capable of inhibiting 80% of T-cell IFN-g production. To assess the role of these LDGs in aGVHD, lethally irradiated (C57BL/6 _ BALB/c) F1 hosts were reconstituted with T celldepleted bone marrow cells plus nylonwoolpurified spleencells 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(AU)