Purpose of review: Several primary immune deficiency disorders are associated with autoimmunity and malignancy, suggesting a state of immune dysregulation. Here, we review the role of regulatory T-cell deficits in mediating the immune dysregulation associated with certain primary immune deficiency disorder syndromes.
Recent findings: Systematic studies in primary immune deficiency disorders and their associated animal models have led to an increased understanding of both central and peripheral tolerance mechanisms, and in particular have yielded new insights into regulatory T-cell function, development and maintenance.
Summary: Single-gene defects identified in patients with multiple autoimmune phenomena have defined new primary immune deficiency disorder syndromes in which the primary deficit is in the establishment or maintenance of immune tolerance. The disorder that has been most informative with regard to understanding the function and development of regulatory T cells is forkhead box P3 deficiency, known as immune dysregulation, polyendocrinopathy, enteropathy and X-linked syndrome in humans and Scurfy in the mouse. Recent studies in patients with other primary immune deficiency disorders, including autoimmune polyendocrinopathy, candidiasis and ectodermal dystrophy syndrome, CD25 deficiency, STAT5b deficiency, and Wiskott-Aldrich syndrome, have added to our understanding of regulatory T-cell biology. The study of patients with rare primary immune deficiency disorder syndromes provides an unparalleled opportunity to understand mechanisms of autoimmunity and immune tolerance in humans.