Regulatory T Cells in Primary Immunodeficiency Diseases

Troy R Torgerson; Hans D Ochs

Disclosures

Curr Opin Allergy Clin Immunol. 2007;7(6):515-521. 

In This Article

Abstract and Introduction

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.

Primary immune deficiency disorders (PIDDs) have traditionally been thought of as defects in the cognate or innate immune system that are characterized primarily by recurrent bacterial, viral and fungal infections. Increasingly, it has been recognized that many of these disorders are associated with a higher incidence of autoimmune diseases and malignancies. This dichotomy of overreaction to self-antigens while lacking a robust response against microorganisms suggests that PIDD patients have a 'dysregulated' immune system resulting in a decreased ability to differentiate between self and foreign antigens. The concept of immune dysregulation as a direct cause of autoimmunity in PIDDs has been strengthened by the recent discovery of distinct clinical entities linked to single gene defects resulting in multiple autoimmune phenomena including immune dysregulation, polyendocrinopathy, enteropathy and X-linked (IPEX) syndrome, autoimmune polyendocrinopathy, candidiasis and ectodermal dystrophy (APECED) syndrome, and autoimmune lymphoproliferative syndrome.[1,2,3]

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