Sadelain M W, Voralia M, Green D R, Wegmann T G
Department of Immunology, University of Alberta, Edmonton, Canada.
J Immunol. 1989 Apr 1;142(7):2270-8.
We report here that bone marrow stem cell engraftment in unirradiated hosts correlates with levels of natural suppressor (NS) activity in the host at the time of transplantation. This is shown in the antibody-facilitated murine chimeras, in which conditioning consists of a single injection of anti-host MHC antibody, which results in long term hemopoietic engraftment in P----F1 and syngeneic donor-host combinations. The data establish that, in two independent situations, engraftment is reduced in hosts with elevated NS activity. Resistance to engraftment in antibody-conditioned adult hosts is increased by prior administration of CFA, which also increases NS activity. Likewise, neonatal animals, which are highly resistant to antibody-facilitated engraftment, exhibit a spontaneously-increased level of NS activity. This resistance declines with the ontogenic waning of splenic NS activity. Conversely, administration of facilitating antibody decreases host bone marrow NS activity, while anti-MHC antibodies that fail to facilitate engraftment do not reduce it. NK activity, on the other hand, correlates poorly with resistance or susceptibility to marrow engraftment in these situations. These results suggest that immunoregulatory functions associated with hemopoiesis may control engraftment of donor stem cells in unirradiated hosts.
我们在此报告，未受辐照宿主中的骨髓干细胞植入与移植时宿主的天然抑制（NS）活性水平相关。这在抗体介导的小鼠嵌合体中得到了证实，在这种嵌合体中，预处理包括单次注射抗宿主MHC抗体，这会导致在P----F1以及同基因供体-宿主组合中实现长期造血植入。数据表明，在两种独立的情况下，NS活性升高的宿主中植入率降低。预先给予CFA会增加抗体预处理成年宿主对植入的抗性，这也会增加NS活性。同样，对抗体介导的植入具有高度抗性的新生动物，其NS活性水平会自发升高。随着脾脏NS活性在个体发育过程中的减弱，这种抗性也会下降。相反，给予促进性抗体可降低宿主骨髓NS活性，而未能促进植入的抗MHC抗体则不会降低它。另一方面，在这些情况下，NK活性与对骨髓植入的抗性或易感性相关性较差。这些结果表明，与造血相关的免疫调节功能可能控制未受辐照宿主中供体干细胞的植入。
