Department of Pediatrics, Division of Allergy and Immunology, Duke University Medical Center, Durham, NC, USA.
Clin Exp Immunol. 2013 Jul;173(1):140-9. doi: 10.1111/cei.12088.
The development of T cells with a regulatory phenotype after thymus transplantation has not been examined previously in complete DiGeorge anomaly (cDGA). Seven athymic infants with cDGA and non-maternal pretransplantation T cell clones were assessed. Pretransplantation forkhead box protein 3 (Foxp3)(+) T cells were detected in five of the subjects. Two subjects were studied in greater depth. T cell receptor variable β chain (TCR-Vβ) expression was assessed by flow cytometry. In both subjects, pretransplantation FoxP3(+) and total CD4(+) T cells showed restricted TCR-Vβ expression. The development of naive T cells and diverse CD4(+) TCR-Vβ repertoires following thymic transplantation indicated successful thymopoiesis from the thymic tissue grafts. Infants with atypical cDGA develop rashes and autoimmune phenomena before transplantation, requiring treatment with immunosuppression, which was discontinued successfully subsequent to the observed thymopoiesis. Post-transplantation, diverse TCR-Vβ family expression was also observed in FoxP3(+) CD4(+) T cells. Interestingly, the percentages of each of the TCR-Vβ families expressed on FoxP3(+) and total CD4(+) T cells differed significantly between these T lymphocyte subpopulations before transplantation. By 16 months post-transplantation, however, the percentages of expression of each TCR-Vβ family became significantly similar between FoxP3(+) and total CD4(+) T cells. Sequencing of TCRBV DNA confirmed the presence of clonally amplified pretransplantation FoxP3(+) and FoxP3(-) T cells. After thymus transplantation, increased polyclonality was observed for both FoxP3(+) and FoxP3(-) cells, and pretransplantation FoxP3(+) and FoxP3(-) clonotypes essentially disappeared. Thus, post-transplantation thymic function was associated with the development of a diverse repertoire of FoxP3(+) T cells in cDGA, corresponding with immunological and clinical recovery.
在完全性 DiGeorge 异常（cDGA）中，先前并未检查过胸腺移植后具有调节表型的 T 细胞的发育情况。评估了 7 名患有 cDGA 且无母体移植前 T 细胞克隆的无胸腺婴儿。在 5 名受试者中检测到了移植前叉头框蛋白 3（Foxp3）（+）T 细胞。对其中 2 名受试者进行了更深入的研究。通过流式细胞术评估 T 细胞受体可变β链（TCR-Vβ）表达。在这两个研究对象中，移植前 FoxP3（+）和总 CD4（+）T 细胞显示出受限的 TCR-Vβ 表达。在胸腺移植后，幼稚 T 细胞和多样化的 CD4（+）TCR-Vβ 谱系的发育表明，来自胸腺组织移植物的成功胸腺发生。具有非典型 cDGA 的婴儿在移植前会出现皮疹和自身免疫现象，需要进行免疫抑制治疗，在观察到胸腺发生后成功停止了治疗。移植后，FoxP3（+）CD4（+）T 细胞中也观察到多样化的 TCR-Vβ 家族表达。有趣的是，在移植前，FoxP3（+）和总 CD4（+）T 细胞上表达的每个 TCR-Vβ 家族的百分比在这些 T 淋巴细胞亚群之间有显著差异。然而，在移植后 16 个月时，FoxP3（+）和总 CD4（+）T 细胞上每个 TCR-Vβ 家族的表达百分比变得非常相似。TCRBV DNA 测序证实了移植前 FoxP3（+）和 FoxP3（-）T 细胞存在克隆扩增。胸腺移植后，FoxP3（+）和 FoxP3（-）细胞均观察到多克隆性增加，移植前的 FoxP3（+）和 FoxP3（-）克隆型基本消失。因此，移植后胸腺功能与 cDGA 中 FoxP3（+）T 细胞多样化的免疫谱的发育相关，与免疫和临床恢复相对应。
