Reconstitution after transplantation with T-lymphocyte-depleted HLA haplotype-mismatched bone marrow for severe combined immunodeficiency.
Reconstitution after transplantation with T-lymphocyte-depleted HLA haplotype-mismatched bone marrow for severe combined immunodeficiency.
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用于治疗严重联合免疫缺陷的 T 淋巴细胞耗尽的 HLA 单倍型不匹配骨髓移植后的重建。
DOI：
10.1073/pnas.79.19.6047
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发表时间：
1982
影响因子：
11.1
通讯作者：
Schlossman,SF
中科院分区：
文献类型：
--
作者：
Reinherz,EL;Geha,R;Rappeport,JM;Wilson,M;Penta,AC;Hussey,RE;Fitzgerald,KA;Daley,JF;Levine,H;Rosen,FS;Schlossman,SF
如果患者有合适的组织相容供者，严重联合免疫缺陷(SCID)有可能通过骨髓移植得到纠正。在缺乏人类白细胞抗原相合供者的情况下，可能会发生由同种异体反应性供者T细胞介导的致死性移植物抗宿主病(GVHD)。为了预防一名缺乏匹配供者的SCID患者的移植物抗宿主病，我们用一种独特的非有丝分裂T细胞特异性单抗(抗T12)和补体治疗单倍体匹配的母亲骨髓，以去除成熟的T细胞。尽管99%以上的成熟T细胞被移除，但该儿童发生了严重的危及生命的移植物抗宿主病，并通过5天的静脉注射抗T12终止了GVHD。随后，免疫重建在6wk时发生：成熟的循环T细胞在体外对可溶性和同种异体抗原的反应而增殖，并为B细胞免疫球蛋白的合成提供帮助。患者被从保护性环境中移出，在没有进一步感染证据的情况下出院。人类白细胞抗原和染色体分析均显示患者的循环细胞来自母体。更重要的是，母体T细胞不再与受体细胞发生反应。混合实验表明，导致这种嵌合体的耐受状态不是由于主动抑制。我们的结论是，如果成熟的同种异体供者T淋巴细胞在骨髓移植前后被耗尽，就可以进行人类白细胞抗原不相合的SCID移植。
Severe combined immunodeficiency (SCID) is potentially correctable by bone marrow transplantation if a patient has a suitable histocompatible donor. In the absence of an HLA-matched donor, lethal graft-versus-host disease (GVHD), which is mediated by alloreactive donor T cells, may occur. In an attempt to prevent GVHD in one SCID patient lacking a matched donor, we treated maternal haplomismatched bone marrow with a unique nonmitogenic T-cell-specific monoclonal antibody (anti-T12) and complement to remove mature T cells. Despite the removal of greater than 99% mature T cells, the child developed significant life-threatening GVHD, which was terminated by a 5-day course of intravenous anti-T12. Subsequently, immune reconstitution occurred by 6 wk: the mature circulating T cells proliferated in response to soluble and allo-antigens in vitro and provided help for B-cell immunoglobulin synthesis. The patient was removed from a protective environment and discharged without evidence of further infection. Both HLA and chromosomal analyses showed that the circulating cells in the patient were of maternal origin. More importantly, the maternal T cells were no longer reactive with recipient cells. Mixing experiments indicated that the state of tolerance that resulted in this chimera was not due to active suppression. We conclude that HLA-mismatched transplantation for SCID can be undertaken if mature alloreactive donor T lymphocytes are depleted before and after bone marrow grafting.