Adriani Marsilio, Aoki Joseph, Horai Reiko, Thornton Angela M, Konno Akihiro, Kirby Martha, Anderson Stacie M, Siegel Richard M, Candotti Fabio, Schwartzberg Pamela L
Genetics and Molecular Biology Branch, National Human Genome Research Institute, National Institutes of Health, 49 Convent Dr., Blg. 49, Rm 3A20, Bethesda, MD 20892-4442, USA.
Clin Immunol. 2007 Jul;124(1):41-8. doi: 10.1016/j.clim.2007.02.001. Epub 2007 May 18.
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.
威斯科特-奥尔德里奇综合征（WAS）是一种原发性免疫缺陷病，其特征是T细胞功能受损与T细胞介导的病理反应过度同时存在，包括自身免疫和湿疹。WAS蛋白（WASp）缺陷小鼠也存在免疫缺陷，并可发生自身免疫性疾病。由于调节性T细胞（Treg）缺陷与自身免疫有关，我们研究了这些细胞在WAS患者和WASp缺陷小鼠中的存在情况和功能。我们发现，在缺乏WASp表达的情况下，CD4(+)CD25(+)FOXP3(+) Treg细胞仍可发育。然而，来自WASp缺陷小鼠以及所研究的五名WAS患者中的四名患者的Treg细胞在体外显示出抑制功能受损。在WASp缺陷小鼠中，这种缺陷可通过用白细胞介素-2进行预激活而部分得到挽救，这表明细胞激活不足可能在WASp缺陷的Treg功能障碍中起作用。这些发现可能为WAS复杂的病理生理学和矛盾的表型提供见解，并为这些患者的自身免疫提出新的治疗方法。
