OKunewick J P, Kociban D L, Machen L L, Buffo M J
Allegheny-Singer Research Institute, Allegheny General Hospital, Pittsburgh, PA 15212, USA.
Bone Marrow Transplant. 1995 Sep;16(3):451-6.
Studies were performed to examine whether, in addition to T cells, there might be other immune cells also capable of exerting a graft-versus-leukemia (GVL) response following allogeneic marrow transplant. Using an MHC-matched mouse model, consisting of normal B10.S donors and SJL/J Rauscher-retroviral-leukemic recipients, the donor cells were selectively depleted of their Asialo-GM1+ component prior to being infused into the leukemic recipients. The incidence of relapse was then compared against that for matched leukemic control recipients of undepleted cells from the same donors. FCM analysis of the depletion protocol indicated that exposure to anti-Asialo-GM1 antibody eliminated more than half of the donor NK1.1+ cells, but caused no significant losses among the Thy-1+, CD3+, or CD8+ cells. Nevertheless, fatal relapse among the leukemic recipients of the depleted cells was nearly double that found among the leukemic control recipients of undepleted cells, 47.5 vs 25.4% (P = 0.01). In a parallel study, using normal SJL/J recipients, this same depletion protocol was found to have no significant effect on the incidence of graft-versus-host disease (GVHD). These results therefore suggest that Asialo-GM1+ NK cells may be capable of contributing to the suppression of relapse in this type of leukemic recipient of allogeneic marrow, and that this suppression may occur independently of GVHD.
开展了多项研究，以检验在同种异体骨髓移植后，除了T细胞之外，是否可能还有其他免疫细胞也能够发挥移植物抗白血病（GVL）反应。使用一种MHC匹配的小鼠模型，该模型由正常的B10.S供体和SJL/J劳氏肉瘤逆转录病毒白血病受体组成，在将供体细胞注入白血病受体之前，选择性去除其去唾液酸GM1+成分。然后将复发率与来自相同供体的未去除细胞的匹配白血病对照受体的复发率进行比较。对去除方案的流式细胞术分析表明，暴露于抗去唾液酸GM1抗体可消除超过一半的供体NK1.1+细胞，但在Thy-1+、CD3+或CD8+细胞中未造成显著损失。然而，去除细胞的白血病受体中的致命复发率几乎是未去除细胞的白血病对照受体中的两倍，分别为47.5%和25.4%（P = 0.01）。在一项平行研究中，使用正常的SJL/J受体，发现相同的去除方案对移植物抗宿主病（GVHD）的发生率没有显著影响。因此，这些结果表明，去唾液酸GM1+ NK细胞可能有助于抑制这种同种异体骨髓白血病受体的复发，并且这种抑制可能独立于GVHD发生。
