Impaired in vitro regulatory T cell function associated with Wiskott-Aldrich syndrome
Impaired in vitro regulatory T cell function associated with Wiskott-Aldrich syndrome
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DOI：
10.1016/j.clim.2007.02.001
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发表时间：
2007-07-01
影响因子：
8.6
通讯作者：
Schwartzberg, Pamela L.
中科院分区：
文献类型：
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作者：
Adriani, Marsilio;Aoki, Joseph;Schwartzberg, Pamela L.
Wiskott-Aldrich综合征（WAS）是一种原发性免疫缺陷，其特征在于受损的T细胞功能和夸大的T细胞介导的病理（包括自身免疫和湿疹）的矛盾共存。WAS蛋白（WASp）缺陷小鼠也是免疫缺陷的，并且可以发展自身免疫性疾病。由于调节性T细胞（Treg）的缺陷与自身免疫相关，我们检查了WAS患者和WASP缺陷小鼠中这些细胞的存在和功能。我们发现CD4（+）CD25（+）FOXP3（+）Treg细胞可以在WASP表达缺失的情况下发育。然而，来自WASP缺陷小鼠和来自五分之四的WAS患者的Treg细胞都显示出体外抑制功能受损。在WASP缺陷型小鼠中，这种缺陷可以通过用IL-2预活化而部分挽救，这表明细胞活化不足可能在WASP缺陷型Treg功能障碍中起作用。这些发现可能提供了深入了解复杂的病理生理学和矛盾的表型WAS，并提出新的治疗模式，在这些患者的自身免疫。爱思唯尔公司出版
Wiskott-Aldrich syndrome (WAS) is a primary immunodeficiency characterized by the contradictory coexistence of impaired T-cell function and exaggerated T-cell-mediated pathology, including autoimmunity and eczema. WAS protein (WASp)-deficient mice are also immunodeficient and can develop autoimmune disease. Since defects in regulatory T-cells (Treg) are associated with autoimmunity, we examined the presence and function of these cells in WAS patients and WASP-deficient mice. We found that CD4(+)CD25(+)FOXP3(+) Treg cells can develop in the absence of WASP expression. However, Treg cells both from WASP-deficient mice and from four out of five WAS patients studied showed impaired in vitro suppressor function. In WASP-deficient mice, this defect could be partially rescued by pre-activation with IL-2, suggesting that inadequate cell activation may play a role in WASP-deficient Treg dysfunction. These findings may provide insights into the complex pathophysiology and paradoxical phenotypes of WAS and suggest new therapeutic modalities for autoimmunity in these patients. Published by Elsevier Inc.