Reconstitution of T-cell compartment after in utero stem cell transplantation: analysis of T-cell repertoire and thymic output.
Reconstitution of T-cell compartment after in utero stem cell transplantation: analysis of T-cell repertoire and thymic output.
复制标题
子宫内干细胞移植后 T 细胞区室的重建：T 细胞库和胸腺输出的分析。
作者：
S. Pirovano;L. Notarangelo;F. Malacarne;E. Mazzolari;F. Porta;A. Lanfranchi;S. Giliani;S. Zucca;S. Pecorelli;A. Albertini;A. Ugazio;L. Imberti
背景和目标
造血干细胞宫内移植可使重度联合免疫缺陷胎儿免疫重建。这项工作的目的是研究该程序后T细胞重建的质量。
设计和方法
我们评估了5名患有严重联合免疫缺陷（SCID）的婴儿的T细胞重建的动力学和程度，其中3名为B+，2名为B-表型，他们在出生前接受了单倍体相合干细胞移植。为此，我们测量了T细胞受体切除环（TREC）的频率和T细胞库的多样性。
结果
子宫内移植导致供体来源的T淋巴细胞植入，在四名健康状况良好的婴儿中达到正常数量。在3例B+表型患者中，异质性T细胞库的产生与TREC水平的发展相关，与接受产后移植治疗的SCID患者和健康婴儿的TREC水平相当。在2例B-表型患者中，1例出现混合T细胞嵌合体和大量循环T细胞，与T细胞库的可变异质性相关;出生后不久TREC水平正常，但此后下降。剩余的B-患者仍为淋巴细胞减少，T细胞库偏斜，TREC水平极低。该患者最终在5岁时需要从匹配的无关供体进行移植，但死于EBV相关的淋巴组织增生性疾病。
解释和结论
这些数据表明，子宫内移植的胎儿与B+ SCID允许新的多样化的T淋巴细胞的产生，并确保长期重建细胞介导的免疫。
BACKGROUND AND OBJECTIVES
In utero transplantation of hematopoietic stem cells allows immune reconstitution of fetuses with severe combined immunodeficiency. The objective of this work was to study the quality of T-cell reconstitution following this procedure.
DESIGN AND METHODS
We evaluated the kinetics and extent of T-cell reconstitution in five infants with severe combined immune deficiency (SCID), three with a B+ and two with a B- phenotype, who received haploidentical stem cell transplantation before birth. To this end, we measured the frequency of T-cell receptor excision circles (TREC) and the diversity of the T-cell repertoire.
RESULTS
In utero transplantation led to engraftment of donor-derived T lymphocytes which attained normal numbers in four infants, who are in good health. In the three patients with a B+ phenotype, generation of a heterogeneous T-cell repertoire was associated with development of TREC levels comparable to those of SCID patients treated by post-natal transplantation and of healthy babies. Of the two patients with a B- phenotype, one developed mixed T-cell chimerism and a substantial number of circulating T cells, associated with a variable heterogeneity of the T-cell repertoire; TREC levels were normal soon after birth, but declined thereafter. The remaining B- patient remained lymphopenic with a skewed T-cell repertoire and very low TREC levels. This patient eventually required transplantation from a matched unrelated donor at 5 years of age, but died of EBV-related lymphoproliferative disease.
INTERPRETATION AND CONCLUSIONS
These data indicate that in utero transplantation of fetuses with B+ SCID allows generation of newly diversified T lymphocytes and ensures long-term reconstitution of cell-mediated immunity.
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影响因子：
20.3
作者：
L. Lum
通讯作者：
L. Lum
DOI：
10.1073/pnas.96.4.1536
发表时间：
1999-02-16
影响因子：
11.1
作者：
Kong, FK;Chen, CLH;Cooper, MD
通讯作者：
Cooper, MD
检测人骨髓移植后记忆抗原的特异性抗体形成。
影响因子：
20.3
作者：
Lum,LG;Munn,NA;Schanfield,MS;Storb,R
通讯作者：
Storb,R
影响因子：
3.6
作者：
Witherspoon,RP;Lum,LG;Storb,R
通讯作者：
Storb,R
人类同种异体骨髓移植后胸腺的病理学。
DOI：
--
发表时间：
1987
期刊：
The American journal of pathology
影响因子：
--
作者：
Müller-Hermelink,HK;Sale,GE;Borisch,B;Storb,R
通讯作者：
Storb,R