Raff R F, Sandmaier B M, Graham T, Loughran T P, Pettinger M, Storb R
Fred Hutchinson Cancer Research Center, Seattle, WA 98104-2092.
Exp Hematol. 1994 Aug;22(9):893-7.
Dogs undergoing rejection of unrelated, dog leukocyte antigen (DLA)-nonidentical marrow grafts show an increase in mononuclear cell counts in the peripheral blood at 1 week after transplant. Cells are of host origin and express phenotypic and morphologic characteristics of large granular lymphocytes (LGLs). LGLs from rejecting dogs suppress in vitro growth of donor marrow colony-forming units-granulocyte/macrophage (CFU-GM) and have natural killer (NK) cell activity. The current study tested whether the marrow-suppressive activity of LGLs obtained at the time of marrow graft rejection was major histocompatibility complex (MHC)-restricted. Five dogs were in the process of rejecting their DLA-nonidentical unrelated marrow grafts after conditioning with 9.2 Gy total-body irradiation (TBI). At the time of rejection, peripheral blood mononuclear cells (PBMC) were harvested. PBMC were co-cultured with marrow obtained from the original marrow transplant donor and from other unrelated dogs that were either DLA-identical or -nonidentical with the marrow donor. A statistically significant reduction of marrow donor CFU-GM was seen when compared to results with autologous effector PBMC from the marrow donor. The number of colonies with recipient effector PBMC ranged from 8 to 75% (median 29%). No suppression was seen with PBMC effectors from unrelated DLA-identical or DLA-nonidentical dogs. Similarly, significant reductions in the number of CFU-GM compared to autologous controls were seen with effector PBMC from marrow recipients and marrow target cells, both from unrelated dogs that were phenotypically DLA-identical or -nonidentical with the marrow donor. The number of colonies ranged from 6 to 68% (median 29%) and 1 to 102% (median 20%), respectively. NK activity was present at low levels in all recipients, while specific alloantigen-primed cytotoxic T cell killing by cells obtained from the five recipients yielded cytolysis of donor PBMC in only one case, suggesting that the marrow-suppressive activity was NK cell-mediated. In conclusion, PBMC from canine marrow transplant recipients undergoing rejection of DLA-nonidentical marrow grafts suppress in vitro CFU-GM growth of marrow donor cells, and this suppression is not MHC-restricted.
接受不相关的、犬白细胞抗原（DLA）不匹配骨髓移植排斥反应的犬，在移植后1周外周血单核细胞计数增加。这些细胞来源于宿主，表现出大颗粒淋巴细胞（LGL）的表型和形态学特征。来自发生排斥反应犬的LGL可在体外抑制供体骨髓粒系/巨噬系集落形成单位（CFU-GM）的生长，并具有自然杀伤（NK）细胞活性。本研究检测了在骨髓移植排斥时获得的LGL的骨髓抑制活性是否受主要组织相容性复合体（MHC）限制。5只犬在接受9.2 Gy全身照射（TBI）预处理后，正处于排斥其DLA不匹配的无关骨髓移植的过程中。在排斥发生时，采集外周血单核细胞（PBMC）。将PBMC与来自原始骨髓移植供体以及其他与骨髓供体DLA相同或不同的无关犬的骨髓共同培养。与来自骨髓供体的自体效应PBMC的结果相比，骨髓供体CFU-GM出现了统计学上的显著减少。接受者效应PBMC形成的集落数量范围为8%至75%（中位数为29%）。来自DLA相同或不同的无关犬的PBMC效应细胞未观察到抑制作用。同样，与自体对照相比，来自骨髓受体和骨髓靶细胞（均来自与骨髓供体在表型上DLA相同或不同的无关犬）的效应PBMC的CFU-GM数量也显著减少。集落数量分别为6%至68%（中位数为29%）和1%至102%（中位数为20%）。所有受体的NK活性水平较低，而从这5只受体获得的细胞对特异性同种抗原致敏细胞毒性T细胞的杀伤作用仅在1例中导致供体PBMC的细胞溶解，这表明骨髓抑制活性是由NK细胞介导的。总之，经历DLA不匹配骨髓移植排斥反应的犬骨髓移植受体的PBMC可在体外抑制骨髓供体细胞的CFU-GM生长，且这种抑制不受MHC限制。
