Acute rejection of allogeneic hemopoietic progenitors by genetically resistant mice.
Acute rejection of allogeneic hemopoietic progenitors by genetically resistant mice.
复制标题
遗传抗性小鼠对同种异体造血祖细胞的急性排斥。
DOI：
10.1002/eji.1830190702
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发表时间：
1989
影响因子：
5.4
通讯作者：
Nakamura,I
中科院分区：
文献类型：
--
作者：
Shimamura,K;Kaminsky,SG;Nakamura,I
对同种异体造血移植物的自然抵抗导致移植物在24-48小时内从宿主体内功能性消除。这种抵抗是特异的，针对未知性质的细胞表面靶标结构。这些决定因素由主要组织相容性复合体连锁的造血组织相容性(HH)基因座控制，并由造血系统的细胞表达。在这项研究中，通过定期取样直接跟踪移植的造血祖细胞的功能存活，检测了各种造血祖细胞的易感性以及早期排斥过程的性质和动力学。在F1杂交系和近交系同种异体宿主中，granulocyte‐erythrocyte‐monocyte‐megakaryocyte系的多潜祖细胞、粒-单核细胞系的双潜祖细胞和红细胞、粒细胞和单核细胞的单潜祖细胞都容易被消除。因此，在有限的比较范围内，无论是血统还是承诺或分化的程度都不能决定造血祖细胞对耐药的易感性。在半固体培养条件下，移植的祖细胞从受体脾中的功能消除是不可逆的。在移植后不久和移植后24小时，抗性宿主和敏感宿主在脾内播种的频率相当，10%的克隆祖细胞仍有功能。自然杀伤细胞的激活加强了先前存在的抵抗力，但并没有将遗传敏感的小鼠转化为抵抗力。因此，抵抗力取决于具有预定特异性的效应器机制。
Natural resistance to hemopoietic allograft results in functional elimination of the graft from the host within 24 to 48 h. The resistance is specific and is directed to the cell surface target structures of an unidentified nature. These determinants are controlled by the major histocompatibility complex‐linked hemopoietic histocompatibility (Hh) loci and expressed by cells of the hemopoietic system. In this study, the susceptibility of various hemopoietic progenitors, as well as the nature and the kinetics of the early rejection process, were examined by directly following the functional survival of the grafted progenitors by periodic sampling. In both F1hybrid and inbred allogeneic hosts, multipotential progenitors for granulocyte‐erythrocyte‐monocyte‐megakaryocyte lineages, bipotential progenitors for granulocyte‐monocyte lineages and unipotential progenitors of erythrocyte, granulocyte and monocyte were susceptible to elimination. Therefore, within the limited range of comparisons, neither the lineage, nor the degree of commitment or differentiation determines the susceptibility of hemopoietic progenitors to resistance. Functional elimination of the grafted progenitors from the recipient spleen was irreversible upon cultivation in semisolid medium. The frequency of seeding in the spleen at 3 h was comparable in resistant and susceptible hosts elimination commenced shortly afterwards and by 24 h after transplantation < 10% of clonogenic progenitors remained functional. Activation of natural killer cells strengthened pre‐existing resistance, but did not convert genetically susceptible mice to resistant. Therefore, the resistance is dependent on an effector mechanism with predetermined specificity.