Patients With Antineutrophil Cytoplasmic Antibody–Associated Vasculitis Have Defective Treg Cell Function Exacerbated by the Presence of a Suppression‐Resistant Effector Cell Population
Open Access
- 1 April 2013
- journal article
- vasculitis
- Published by Wiley in Arthritis & Rheumatism
- Vol. 65 (7), 1922-1933
- https://doi.org/10.1002/art.37959
Abstract
Objective The development of pathogenic antineutrophil cytoplasmic antibodies (ANCAs) can result in systemic small vessel vasculitis. However, the breakdown in immune tolerance that results in the induction and persistence of ANCAs is not well understood. We undertook this study to test our hypothesis that abnormal T cell regulation is central to disease pathogenesis in patients with ANCA‐associated vasculitis (AAV). Methods Peripheral blood samples were obtained from 62 patients with AAV and 19 healthy controls for flow cytometric analysis of CD4+ T cell populations. Functional T cell studies were performed with fluorescence‐activated cell sorted CD4+ T cell populations stimulated with anti‐CD3/anti‐CD28. Results We demonstrated two separate abnormalities in T cell regulation in patients with AAV. First, we showed that the Treg cell frequency was increased in the peripheral blood of patients with active disease, but Treg cells from patients with AAV had decreased suppressive function. Treg cells from patients with active disease disproportionately used a FoxP3 isoform lacking exon 2, which might alter Treg cell function. Second, we identified a CD4+ T cell population with increased frequency that was resistant to Treg cell suppression, produced proinflammatory cytokines, and was antigen experienced. Conclusion AAV is associated with disruption of the suppressive Treg cell network and with increased frequency of a distinct proinflammatory effector T cell subset that comprises the majority of peripheral CD4+ T cells.Keywords
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