Wahn V, Yokota S, Meyer K L, Janssen J W, Hansen-Hagge T E, Knobloch C, Koletzko S, Stein H, Friedrich W, Bartram C R
Universitäts-Kinderklinik, Düsseldorf, FRG.
J Immunol. 1991 Nov 1;147(9):2934-41.
The diagnosis of severe combined immunodeficiency complicated by chronic graft-vs-host disease affecting liver and skin in association with engraftment of maternal T cells was established in a 5-mo-old boy. Detailed immunologic and molecular genetic studies were performed because a unique T cell phenotype was identified on initial evaluation. A major proportion of the patient's peripheral T cells expressed a CD8+ and TCR-gamma/delta+ phenotype while CD4+ T cells were virtually absent. Southern blot analysis of cell subpopulations isolated by fluorescence activated cell sorting indicated that approximately 50% of CD8+/TCR-gamma/delta+ cells were clonally related. Immunophenotyping and -genotyping also identified a clonal TCR-gamma/delta+ cell population in the child's mother. Clonal identity of these T cell populations in mother and child was demonstrated by studies using a clonspecific TCR-delta probe generated by polymerase chain reaction as well DNA sequence analysis. HLA typing and DNA fingerprinting confirmed that the child had acquired this clone diaplacentally from the mother. According to immunohistology and DNA analysis the clone was found to be virtually absent in the liver tissue suggesting that this clonal T cell population plays a minor role, if any, in the pathogenesis of the liver abnormalities in the patient. In the mother the CD8+/TCR-gamma/delta+ clone spontaneously declined to a level around 1% of PBMC several months later and has remained at this level since. We conclude that 1) a clonal expansion of TCR-gamma/delta T cells, triggered by yet unknown stimuli, may occur in otherwise healthy individuals, 2) respective T cells are able to cross the placental barrier, and 3) in an microenvironment precluding rejection, i.e., in severely immunocompromised patients, these cells may persist and even represent a significant proportion of circulating T cells.
一名5个月大的男童被诊断为重症联合免疫缺陷合并慢性移植物抗宿主病，累及肝脏和皮肤，并伴有母源T细胞植入。由于在初始评估中发现了独特的T细胞表型，因此进行了详细的免疫学和分子遗传学研究。患者外周血T细胞的主要部分表达CD8⁺和TCR-γ/δ⁺表型，而CD4⁺T细胞几乎不存在。通过荧光激活细胞分选分离的细胞亚群的Southern印迹分析表明，约50%的CD8⁺/TCR-γ/δ⁺细胞具有克隆相关性。免疫表型分析和基因分型还在患儿母亲体内鉴定出一个克隆性TCR-γ/δ⁺细胞群。通过使用聚合酶链反应生成的克隆特异性TCR-δ探针以及DNA序列分析，证实了母婴体内这些T细胞群的克隆同一性。HLA分型和DNA指纹分析证实，患儿经胎盘从母亲那里获得了这个克隆。根据免疫组织学和DNA分析，发现肝脏组织中几乎不存在该克隆，这表明该克隆性T细胞群在患者肝脏异常的发病机制中即使有作用，也起次要作用。几个月后，母亲体内的CD8⁺/TCR-γ/δ⁺克隆自发下降至外周血单个核细胞的1%左右，并自此一直维持在这个水平。我们得出以下结论：1）在其他方面健康的个体中，可能会因未知刺激引发TCR-γ/δ T细胞的克隆性扩增；2）相应的T细胞能够穿过胎盘屏障；3）在排除排斥反应的微环境中，即在严重免疫受损的患者中，这些细胞可能持续存在，甚至占循环T细胞的很大比例。
