Bone Marrow Clonogenic Capability, Cytokine Production, and Thymic Output in Patients with Common Variable Immunodeficiency1
Bone Marrow Clonogenic Capability, Cytokine Production, and Thymic Output in Patients with Common Variable Immunodeficiency1
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常见变异型免疫缺陷患者的骨髓克隆形成能力、细胞因子产生和胸腺输出1
作者：
A. Isgrò;M. Marziali;I. Mezzaroma;G. Luzi;A. Mazzone;V. Guazzi;G. Andolfi;B. Cassani;A. Aiuti;F. Aiuti
在原发性Ab缺乏的患者中，经常观察到血液学和免疫学异常。造血干细胞/祖细胞再生失败已被假设。我们通过集落形成细胞（CFC）和长期培养（LTC）试验评估了11例常见可变免疫缺陷患者骨髓（BM）中BM祖细胞的表型及其体外生长。与健康对照相比，在患者中观察到红细胞和混合CFC显著减少，在更大程度上，原始LTC-CFC祖细胞显著减少。骨髓前b细胞和前b细胞的频率与CD19+淋巴细胞的绝对数量直接相关。与对照组相比，体外培养的BM细胞自发产生较低量的IL-2和较高水平的TNF-α，表明偏向于促凋亡细胞因子模式。此外，BM LTC后生成的基质细胞分泌较少的IL-7，免疫组织化学显示表型改变。这些发现与外周血中共表达CD31的幼稚Th细胞显著减少有关。这些结果表明，在常见的变异性免疫缺陷患者中，祖细胞的生长和分化能力受损。
In patients with primary Ab deficiencies, hematological and immunological abnormalities are frequently observed. A regenerative failure of hemopoietic stem/progenitor cells has been hypothesized. We evaluated in the bone marrow (BM) of 11 patients with common variable immunodeficiency, the phenotype of BM progenitors and their in vitro growth by colony-forming cell (CFC) and long-term culture (LTC) assays. A significant decrease in erythroid and mixed CFC and, to a greater extent, in primitive LTC-CFC progenitors was observed in patients compared with healthy controls. The frequency of BM pre-B and pro-B cells correlated directly with the absolute number of CD19+ lymphocytes. BM cells cultured in vitro produced spontaneously lower amounts of IL-2 and elevated levels of TNF-α compared with controls, indicating a skewing toward a proapoptotic cytokine pattern. In addition, stromal cells generated after BM LTC secreted less IL-7 and displayed by immunohistochemistry an altered phenotype. These findings were associated with a significant decrease in naive Th cells coexpressing CD31 in the peripheral blood. These results indicate an impaired growth and differentiation capacity of progenitor cells in patients with common variable immunodeficiency.