Impaired in vitro regulatory T cell function associated with Wiskott-Aldrich syndrome

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.