Thymic output, T-cell diversity, and T-cell function in long-term human SCID chimeras
Thymic output, T-cell diversity, and T-cell function in long-term human SCID chimeras
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DOI：
10.1182/blood-2009-01-199323
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发表时间：
2009-08-13
期刊：
影响因子：
20.3
通讯作者：
Buckley, Rebecca H.
中科院分区：
文献类型：
--
作者：
Sarzotti-Kelsoe, Marcella;Win, Chan M.;Buckley, Rebecca H.
严重联合免疫缺陷（SCID）是一种由多种遗传原因引起的综合征，其特征是T、B细胞功能严重缺陷，有时还包括NK细胞功能严重缺陷。非消融性人类白细胞抗原相同或严格T细胞去除的单倍体相合亲本骨髓移植（BMT）导致受者中胸腺依赖性遗传供体T细胞发育，从而导致长期存活。我们以前报道过，正常的T细胞数量，功能，和库开发的SCID患者移植后3至4个月，和库保持高度多样性的前10年后BMT。T细胞受体多样性与T细胞受体切除环水平呈正相关，反映了胸腺输出。然而，骨髓移植后10至12年后，SCID患者胸腺功能的命运仍有待确定。在这项超过25年的随访研究中，128例患有11种不同分子类型的SCID患者接受非条件BMT后，我们提供了T细胞功能，胸腺输出和T细胞克隆多样性长期维持的证据。（Blood.2009;114：1445-1453）
Severe combined immunodeficiency (SCID) is a syndrome of diverse genetic cause characterized by profound deficiencies of T, B, and sometimes NK-cell function. Nonablative human leukocyte antigen-identical or rigorously T cell-depleted haploidentical parental bone marrow transplantation (BMT) results in thymus-dependent genetically donor T-cell development in the recipients, leading to long-term survival. We reported previously that normal T-cell numbers, function, and repertoire developed by 3 to 4 months after transplantation in SCID patients, and the repertoire remained highly diverse for the first 10 years after BMT. The T-cell receptor diversity positively correlated with T-cell receptor excision circle levels, a reflection of thymic output. However, the fate of thymic function in SCID patients beyond 10 to 12 years after BMT remained to be determined. In this greater than 25-year follow-up study of 128 patients with 11 different molecular types of SCID after nonconditioned BMT, we provide evidence that T-cell function, thymic output, and T-cell clonal diversity are maintained long-term. (Blood.2009;114:1445-1453)