In humans, mutation of the gene encoding a protein known as WASp leads to susceptibility to infections and systemic autoimmunity. Most studies have focused on understanding the defects in T cell activation caused by the WASp deficiency, but researchers at the University of Washington in Seattle have now found that in mice and humans a population of T cells known as regulatory T cells (Treg), which keep other immune cells from attacking the body's own tissues and causing autoimmunity, are also impaired in the absence of WASp.
In the study, which appears online on January 11 in advance of publication in the February print issue of the Journal of Clinical Investigation, David Rawlings and colleagues show that like WASp-deficient humans, WASp-deficient mice develop systemic autoimmune disease. This was not due to a defect in the number of Treg that developed in the mice, but due to a defect in their ability to control autoimmunity. Consistent with this, the peripheral blood of a WASp-deficient patient in whom a spontaneous revertant mutation occurred had substantial numbers of WASp+ Treg. These cells were able to ameliorate this individual's recurrent episodes of autoimmune hemolytic anemia, indicating that a defect in Treg function is likely to contribute to the systemic autoimmunity from which individuals lacking WASp suffer.
TITLE: Wiskott-Aldrich syndrome protein is required for regulatory T cell homeostasis
AUTHOR CONTACT:
David J. Rawlings
University of Washington School of Medicine, Seattle, Washington, USA.
Phone: (206) 987-7450; Fax: (206) 987-7310; E-mail: drawling@u.washington.edu .
Jennifer Seymour
Media Relations Manager
Children's Hospital and Regional Medical Center, Seattle, Washington, USA.
Phone: (206) 987-5207; Fax: (206) 987-5215; E-mail: jennifer.seymour@seattlechildrens.org
View the PDF of this article at: https://www.the-jci.org/article.php?id=29539
Journal of Clinical Investigation