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

doi:10.1084/jem.20032158

Published online 26 April 2004 doi:10.1084/jem.20032158
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 199, Number 9, 1285-1291

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

Martin A. Kriegel¹, Tobias Lohmann², Christoph Gabler¹, Norbert Blank¹, Joachim R. Kalden¹, and Hanns-Martin Lorenz¹

¹ Department of Medicine III, Institute for Clinical Immunology and Rheumatology
² Section of Endocrinology, Department of Medicine I, University of Erlangen-Nuremberg, 91054 Erlangen, Germany

Address correspondence to Martin A. Kriegel at his present address Section of Immunobiology, TAC S-560, Yale University School of Medicine, 300 Cedar St., P.O. Box 208011, New Haven, CT 06520. Phone: (203) 785-5383; Fax: (203) 737-2958; email: MartinKriegel{at}hotmail.com

In autoimmune polyglandular syndromes (APS), several organ-specificautoimmune diseases are clustered. Although APS type I is causedby loss of central tolerance, the etiology of APS type II (APS-II)is currently unknown. However, in several murine models, depletionof CD4⁺ CD25⁺ regulatory T cells (T_regs) causes a syndrome resemblinghuman APS-II with multiple endocrinopathies. Therefore, we hypothesizedthat loss of active suppression in the periphery could be ahallmark of this syndrome. T_regs from peripheral blood of APS-II,control patients with single autoimmune endocrinopathies, andnormal healthy donors showed no differences in quantity (exceptfor patients with isolated autoimmune diseases), in functionallyimportant surface markers, or in apoptosis induced by growthfactor withdrawal. Strikingly, APS-II T_regs were defective intheir suppressive capacity. The defect was persistent and notdue to responder cell resistance. These data provide novel insightsinto the pathogenesis of APS-II and possibly human autoimmunityin general.

Key Words: suppressor cells • autoimmune polyendocrinopathies • Addison's disease • type I diabetes • autoimmune thyroiditis

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