Defective Suppressor Function of Human CD4+ CD25+ Regulatory T Cells in Autoimmune Polyglandular Syndrome Type II

Overview

Journal J Exp Med

Specialties Allergy & Immunology
General Medicine

Date 2004 May 1

PMID 15117972

Citations 84

Authors

Martin A Kriegel

Tobias Lohmann

Christoph Gabler

Norbert Blank

Joachim R Kalden

Hanns-Martin Lorenz

Affiliations

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Abstract

In autoimmune polyglandular syndromes (APS), several organ-specific autoimmune diseases are clustered. Although APS type I is caused by loss of central tolerance, the etiology of APS type II (APS-II) is currently unknown. However, in several murine models, depletion of CD4(+) CD25(+) regulatory T cells (T(regs)) causes a syndrome resembling human APS-II with multiple endocrinopathies. Therefore, we hypothesized that loss of active suppression in the periphery could be a hallmark of this syndrome. T(regs) from peripheral blood of APS-II, control patients with single autoimmune endocrinopathies, and normal healthy donors showed no differences in quantity (except for patients with isolated autoimmune diseases), in functionally important surface markers, or in apoptosis induced by growth factor withdrawal. Strikingly, APS-II T(regs) were defective in their suppressive capacity. The defect was persistent and not due to responder cell resistance. These data provide novel insights into the pathogenesis of APS-II and possibly human autoimmunity in general.

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