T-lymphocyte differentiation in vitro in severe combined immunodeficiency. Defects of stem cells.
T-lymphocyte differentiation in vitro in severe combined immunodeficiency. Defects of stem cells.
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严重联合免疫缺陷中 T 淋巴细胞的体外分化。
DOI：
10.1172/jci109625
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发表时间：
1979
期刊：
影响因子：
--
通讯作者：
R. Good
中科院分区：
文献类型：
--
作者：
R. Pahwa;S. Pahwa;R. Good
利用正常胸腺上皮单层及其培养上清作为诱导剂，对正常志愿者和11例严重联合免疫缺陷（SCID）患者的分离骨髓细胞进行了t淋巴细胞分化的研究。正常骨髓细胞与胸腺上皮单层或其培养上代共培养后，可有规律地诱导携带人t淋巴细胞抗原（HTLA），与绵羊红细胞形成莲座（E莲座），并对有丝分裂原concanavalin A （Con A）产生应答。相比之下，对SCID患者骨髓细胞的T细胞分化的研究揭示了不同的缺陷，从完全“缺乏”可定义的T细胞前体到部分分化导致T淋巴细胞获得一个（HTLA）或两个（HTLA和E玫瑰座）标记物。只有一名患者诱导了所有三种T细胞标记物，即HTLA、E莲座和对Con a的反应性。这些观察结果表明，SCID是一种异质性疾病，在这种疾病中，分化缺陷可能发生在一个或多个分化位点，导致临床表达T细胞和b细胞功能障碍。此外，我们的研究表明，在t细胞分化过程中，HTLA可能出现在形成e -莲座的能力之前，后者的能力发展之后是对有丝分裂原的反应状态。在SCID中，我们提出了一种伴随前体T细胞缺陷的正常分化方案。
A study of T-lymphocyte differentiation was made on fractionated bone marrow cells from normal volunteers and from 11 patients with severe combined immunodeficiency (SCID) using normal thymic epithelial monolayers and their culture supernates as inducing agents. Normal marrow cells could regularly be induced to bear the human T-lymphocyte antigen (HTLA), to form rosettes with sheep erythrocytes (E rosettes), and to respond to the mitogen concanavalin A (Con A) after coculture with the thymic epithelial monolayers or their culture supernates. In contrast, studies of T-cell differentiation on the marrow cells of patients with SCID revealed varying defects, ranging from a complete "absence" of definable T-cell precursors to partial differentiation resulting in acquisition of one (HTLA) or two (HTLA and E rosettes) markers for T lymphocytes. Only in one patient was there induction of all three T-cell markers, namely, HTLA, E rosettes, and responsiveness to Con A. These observations indicate that SCID is a heterogeneous disorder in which defects of differentiation can occur at one or more multiple sites of differentiation leading the the clinical expression of T- and B-cell dysfunction. Further, our studies indicate that in T-cell differentiation, HTLA probably appears before the capacity to form E-rosettes, and development of the latter capacity is followed by a state of responsiveness to mitogens. A scheme of normal differentiation along with the defects of precursor T cells seen in SCID is presented.