Buckley R H, Whisnant K J, Schiff R I, Gilbertsen R B, Huang A T, Platt M S
N Engl J Med. 1976 May 13;294(20):1076-81. doi: 10.1056/NEJM197605132942002.
As an alternative to bone-marrow transplantation, two infants with severe combined immunodeficiency who had no histocompatible donors were given intraperitoneal infusions of fresh liver cells from fetuses of eight and nine to 10 weeks. Transient graft-versus-host disease began at 42 and 52 days, respectively. Both infants had rises in T cells and declines in B cells by three months. No functional immunologic improvement occurred in the first infant, who died of pulmonary disease 10 months later. Clinical and functional immunologic improvement occurred in the other, who is now 19 months after transplantation. Lymphocyte responses to phytohemagglutinin and pokeweed mitogen were noted by three months, to concanavalin A by five months, and to allogeneic cells by eight months. Delayed cutaneous responsiveness to candida developed and IgM became norma. IgA and IgG remained low. Chimerism was demonstrated by a donor marker chromosome in metaphases from recipient lymphocytes. Fetal liver cells therefore reversed the immunodeficiency.
作为骨髓移植的替代方法,两名患有严重联合免疫缺陷且没有组织相容性供体的婴儿接受了腹腔内输注来自8周和9至10周胎儿的新鲜肝细胞。移植物抗宿主病分别在42天和52天开始出现。到三个月时,两名婴儿的T细胞均增多,B细胞均减少。第一名婴儿没有出现功能性免疫改善,10个月后死于肺部疾病。另一名婴儿出现了临床和功能性免疫改善,现在移植后已有19个月。三个月时观察到淋巴细胞对植物血凝素和商陆有丝分裂原的反应,五个月时对刀豆球蛋白A有反应,八个月时对同种异体细胞有反应。对念珠菌的迟发性皮肤反应出现,IgM恢复正常。IgA和IgG仍较低。通过受体淋巴细胞中期的供体标记染色体证实了嵌合体的存在。因此,胎儿肝细胞逆转了免疫缺陷。