Sykes Megan
Columbia Center for Translational Immunology, Columbia University Medical Center, NY, USA; Department of Medicine, Columbia University Medical Center, NY, USA; Department of Microbiology & Immunology, Columbia University Medical Center, NY, USA; Department of Surgery, Columbia University Medical Center, NY, USA.
Hum Immunol. 2018 May;79(5):334-342. doi: 10.1016/j.humimm.2017.12.011. Epub 2017 Dec 28.
This review focuses on mechanistic studies performed in recipients of non-myeloablative bone marrow transplant regimens developed at Massachusetts General Hospital in HLA-identical and HLA-mismatched haploidentical combinations, initially as a platform for treatment of hematologic malignancies with immunotherapy in the form of donor leukocyte infusions, and later in combination with donor kidney transplantation for the induction of allograft tolerance. In patients with permanent mixed chimerism, central deletion may be a major mechanism of long-term tolerance. In patients in whom donor chimerism is only transient, the kidney itself plays a significant role in maintaining long-term tolerance. A high throughput sequencing approach to identifying and tracking a significant portion of the alloreactive T cell receptor repertoire has demonstrated biological significance in transplant patients and has been useful in pointing to clonal deletion as a long-term tolerance mechanism in recipients of HLA-mismatched combined kidney and bone marrow transplants with only transient chimerism.
本综述聚焦于在麻省总医院开展的非清髓性骨髓移植方案受者中进行的机制研究，这些方案采用 HLA 相同和 HLA 错配的单倍型相同组合，最初作为通过供体白细胞输注形式的免疫疗法治疗血液系统恶性肿瘤的平台，后来与供体肾移植联合用于诱导移植耐受。在具有永久性混合嵌合体的患者中，中枢性缺失可能是长期耐受的主要机制。在供体嵌合体仅为短暂性的患者中，肾脏本身在维持长期耐受中发挥重要作用。一种用于识别和追踪大部分同种异体反应性 T 细胞受体库的高通量测序方法已在移植患者中显示出生物学意义，并有助于指出克隆性缺失是 HLA 错配的肾和骨髓联合移植且仅具有短暂嵌合体的受者中的一种长期耐受机制。
