Schiff S E, Buckley R H
J Immunol. 1987 Apr 1;138(7):2088-94.
After administration of haploidentical stem cells to infants with severe combined immunodeficiency disease (SCID), mature T cells of donor karyotype appear later in the recipient without causing graft-vs-host disease (GVHD). To investigate the effect of the host microenvironment on these genetically donor T cells, mixed leukocyte cultures were carried out. Unfractionated mononuclear cells (MNC) from eight infants with SCID immunologically reconstituted by haploidentical bone marrow stem cells responded in the same pattern as MNC from non-chimeric individuals to autologous and allogeneic irradiated MNC, even though they contained all genetically donor T cells and all genetically patient B cells and monocytes. This included surprisingly vigorous proliferative responses of the patients' MNC to the original donors' irradiated MNC. This autoreactivity could be detected as soon as T cell function appeared post-transplantation and appeared to increase with time. It could be blocked by the addition of monoclonal antibodies to HLA Class II antigens. Responses of most patients' MNC were similar whether stimulated by irradiated MNC from the donor or non-donor parent or by those from unrelated normal controls. Purified genetically donor T cells that had matured from stem cells in the patient's microenvironment responded vigorously to purified donor B cells. These same cells responded much less to patient B cells. In six cases, such genetically donor T cells responded less to patient B cells than fresh donor T cells did to donor B cells in the autologous mixed leukocyte response. By contrast, T cells of donor karyotype from three of the patients responded more vigorously to donor B cells than fresh donor T cells did. Thus, genetically donor T lymphocytes that had matured from stem cells in the recipient microenvironment behaved differently from those that had matured in the donor. The hyporesponsiveness of genetically donor T cells from the patient to patient B cells does not appear to be due to T suppressor cells.
给患有严重联合免疫缺陷病（SCID）的婴儿输注单倍体相合干细胞后，供体核型的成熟T细胞在受者体内较晚出现，且不会引发移植物抗宿主病（GVHD）。为研究宿主微环境对这些基因上为供体的T细胞的影响，进行了混合淋巴细胞培养。来自8名经单倍体相合骨髓干细胞进行免疫重建的SCID婴儿的未分离单核细胞（MNC），对自体和异体照射的MNC的反应模式与非嵌合体个体的MNC相同，尽管它们含有所有基因上为供体的T细胞以及所有基因上为患者的B细胞和单核细胞。这包括患者的MNC对原始供体照射的MNC出人意料地强烈的增殖反应。这种自身反应性在移植后T细胞功能出现时即可检测到，并且似乎随时间增加。添加针对HLA II类抗原的单克隆抗体可阻断这种反应。大多数患者的MNC无论是受到来自供体或非供体亲本的照射MNC刺激，还是受到来自无关正常对照的照射MNC刺激，反应都相似。在患者微环境中从干细胞成熟的纯化的基因上为供体的T细胞对纯化的供体B细胞有强烈反应。这些相同的细胞对患者B细胞的反应则小得多。在6例中，这种基因上为供体的T细胞对患者B细胞的反应比新鲜供体T细胞在自体混合淋巴细胞反应中对供体B细胞的反应小。相比之下，3例患者中具有供体核型的T细胞对供体B细胞的反应比新鲜供体T细胞更强烈。因此，在受者微环境中从干细胞成熟的基因上为供体的T淋巴细胞的行为与在供体内成熟的T淋巴细胞不同。患者体内基因上为供体的T细胞对患者B细胞的低反应性似乎不是由于T抑制细胞所致。
