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Blood. 2010 May 27;115(21):4293-301. doi: 10.1182/blood-2009-05-222190. Epub 2010 Mar 16.

NK cells mediate reduction of GVHD by inhibiting activated, alloreactive T cells while retaining GVT effects.

Author information

1
Department of Medicine, Division of Blood and Marrow Transplantation, Stanford University, CA 94305, USA.

Abstract

Natural killer (NK) cells suppress graft-versus-host disease (GVHD) without causing GVHD themselves. Our previous studies demonstrated that allogeneic T cells and NK cells traffic similarly after allogeneic bone marrow transplantation (BMT). We therefore investigated the impact of donor NK cells on donor alloreactive T cells in GVHD induction. Animals receiving donor NK and T cells showed improved survival and decreased GVHD score compared with controls receiving donor T cells alone. Donor T cells exhibited less proliferation, lower CD25 expression, and decreased interferon-gamma (IFN-gamma) production in the presence of NK cells. In vivo, we observed perforin- and Fas ligand (FasL)-mediated reduction of donor T cell proliferation and increased T cell apoptosis in the presence of NK cells. Further, activated NK cells mediated direct lysis of reisolated GVHD-inducing T cells in vitro. The graft-versus-tumor (GVT) effect was retained in the presence of donor NK cells. We demonstrate a novel mechanism of NK cell-mediated GVHD reduction whereby donor NK cells inhibit and lyse autologous donor T cells activated during the initiation of GVHD.

PMID:
20233969
PMCID:
PMC2879101
DOI:
10.1182/blood-2009-05-222190
[Indexed for MEDLINE]
Free PMC Article
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