Tjønnfjord G E, Steen R, Veiby O P, Friedrich W, Egeland T
Institute of Transplantation Immunology and Medical Department A, The National Hospital, University of Oslo, Norway.
Blood. 1994 Nov 15;84(10):3584-9.
Severe combined immunodeficiencies (SCID), a heterogeneous group of disorders of infancy, are fatal without treatment directed at immunologic reconstitution. Allogeneic bone marrow transplantation (BMT), which is such a treatment presents some unique features in SCID, especially when T-lymphocyte-depleted HLA haploidentical allografts are used. Donor-type T lymphopoiesis, less often B lymphopoiesis, develops, whereas myelopoiesis remains the recipient-type. Little is known about the engrafting cells in this peculiar lymphohematopoietic chimerism and the pathophysiology of the frequent failure of B-lymphocyte reconstitution. To address these issues, we purified CD34+ BM cells from a patient with selective T-lymphocyte reconstitution after HLA haploidentical BMT for B-SCID. Phenotypic analysis of CD34+ cells was performed by flow cytometry, and functional studies of donor- and recipient-type CD34+ cells were performed in vitro. Donor-type CD34+ cells, constituting approximately 2% of the CD34+ cells, were detected; both CD34+ HLA-DR- cells and CD34+ cells coexpressing B-(CD10 and CD19) and T-(CD2 and CD7) lymphocyte-associated cell surface molecules. Donor-type CD34+ cells coexpressing myeloid-associated molecules (CD13, CD14, CD15, and CD33) were undetectable. However, donor-type CD34+ myeloid progenitors could be shown in functional assays. Recipient-type CD34+ cells coexpressing B- and T-lymphocyte- as well as myeloid-associated molecules were detected, but recipient-type CD34+ cells could not be driven into T-lymphocyte differentiation in vitro. These findings provide evidence for engraftment of multipotent stem cells in our patient with B-SCID. Furthermore, the failure of B-lymphocyte reconstitution cannot be explained by lack of donor-type B-lymphocyte progenitors. Donor-type B lymphopoiesis and myelopoiesis are prevented by an unidentified mechanism.
重症联合免疫缺陷（SCID）是一组婴儿期的异质性疾病，若不进行针对免疫重建的治疗则会致命。同种异体骨髓移植（BMT）作为这样一种治疗方法，在SCID中呈现出一些独特特征，尤其是当使用去除T淋巴细胞的HLA单倍型相合同种异体移植物时。供体型T淋巴细胞生成，较少见B淋巴细胞生成会发生，而髓系生成仍为受体型。对于这种特殊的淋巴造血嵌合体中的植入细胞以及B淋巴细胞重建频繁失败的病理生理学知之甚少。为了解决这些问题，我们从一名在接受HLA单倍型相合BMT治疗B - SCID后出现选择性T淋巴细胞重建的患者中纯化了CD34⁺骨髓细胞。通过流式细胞术对CD34⁺细胞进行表型分析，并在体外对供体型和受体型CD34⁺细胞进行功能研究。检测到供体型CD34⁺细胞，约占CD34⁺细胞的2%；CD34⁺ HLA - DR⁻细胞以及共表达B（CD10和CD19）和T（CD2和CD7）淋巴细胞相关细胞表面分子的CD34⁺细胞。未检测到共表达髓系相关分子（CD13、CD14、CD15和CD33）的供体型CD34⁺细胞。然而，在功能试验中可以显示出供体型CD34⁺髓系祖细胞。检测到共表达B和T淋巴细胞以及髓系相关分子的受体型CD34⁺细胞，但受体型CD34⁺细胞在体外不能被诱导分化为T淋巴细胞。这些发现为我们的B - SCID患者中多能干细胞的植入提供了证据。此外，B淋巴细胞重建失败不能用缺乏供体型B淋巴细胞祖细胞来解释。供体型B淋巴细胞生成和髓系生成被一种不明机制所阻止。
