Ogasawara Kouetsu, Benjamin Jonathan, Takaki Rayna, Phillips Joseph H, Lanier Lewis L
Department of Microbiology & Immunology and the Cancer Research Institute, University of California, San Francisco, California 94143-0414, USA.
Nat Immunol. 2005 Sep;6(9):938-45. doi: 10.1038/ni1236. Epub 2005 Aug 7.
Irradiation-resistant natural killer (NK) cells in an F(1) recipient can reject parental bone marrow, and host NK cells can also prevent engraftment of allogeneic bone marrow. We show here that repopulating bone marrow cells in certain mouse strains expressed retinoic acid early inducible 1 proteins, which are ligands for the activating NKG2D NK cell receptor. Treatment with a neutralizing antibody to NKG2D prevented rejection of parental BALB/c bone marrow in (C57BL/6 x BALB/c) F(1) recipients and allowed engraftment of allogeneic BALB.B bone marrow in C57BL/6 recipients. Additionally, bone marrow from C57BL/6 mice transgenic for retinoic acid early inducible 1epsilon was rejected by syngeneic mice but was accepted after treatment with antibody to NKG2D. If other stem cells or tissues upregulate expression of NKG2D ligands after transplantation, NKG2D may contribute to graft rejection in immunocompetent hosts.
F1受体中具有辐射抗性的自然杀伤(NK)细胞能够排斥亲代骨髓,宿主NK细胞也能阻止异基因骨髓的植入。我们在此表明,某些小鼠品系中参与骨髓再填充的细胞在早期表达视黄酸早期诱导1蛋白,该蛋白是激活型NKG2D NK细胞受体的配体。用抗NKG2D中和抗体处理可防止(C57BL/6×BALB/c)F1受体排斥亲代BALB/c骨髓,并使异基因BALB.B骨髓在C57BL/6受体中得以植入。此外,转染视黄酸早期诱导1ε的C57BL/6小鼠的骨髓被同基因小鼠排斥,但在用抗NKG2D抗体处理后被接受。如果其他干细胞或组织在移植后上调NKG2D配体的表达,NKG2D可能会导致免疫活性宿主中的移植物排斥反应。