Patients treated with high‐dose intravenous immunoglobulin show selective activation of regulatory T cells. (4th July 2013)

• Record Type: Journal Article
• Authors: Tjon, A. S. W.; Tha‐In, T.; Metselaar, H. J.; van, R.; van der, L. J. W.; Groothuismink, Z. M. A.; te, P. A. W.; van, P. M.; Kwekkeboom, J.
• Is Part Of: Clinical and experimental immunology. Volume 173:Number 2(2013:Aug.)
• Page Start: 259
• Page End: 267
• Publication Date: 2013-07-04
• Subjects: Immunopathology -- Periodicals; 616.079
• DOI: 10.1111/cei.12102
• Languages: English
• ISSNs: 0009-9104

Abstract

<abstract abstract-type="main"> <title>Summary</title> <p>Intravenous immunoglobulin (IVIg) is used to treat autoimmune and systemic inflammatory diseases caused by derailment of humoral and cellular immunity. In this study we investigated whether IVIg treatment can modulate regulatory T cells (T<sub>regs</sub>) in humans <italic>in vivo</italic>. Blood was collected from IVIg‐treated patients with immunodeficiency or autoimmune disease who were treated with low‐dose (<italic>n</italic> = 12) or high‐dose (<italic>n</italic> = 15) IVIg before, immediately after and at 7 days after treatment. Percentages and activation status of circulating CD4<sup>+</sup>CD25<sup>+</sup>forkhead box protein 3 (FoxP3<sup>+</sup>) T<sub>regs</sub> and of conventional CD4<sup>+</sup>FoxP3<sup>−</sup> T‐helper cells (T<sub>conv</sub>) were measured. The suppressive capacity of T<sub>regs</sub> purified from blood collected at the time‐points indicated was determined in an <italic>ex‐vivo</italic> assay. High‐dose, but not low‐dose, IVIg treatment enhanced the activation status of circulating T<sub>regs</sub>, as shown by increased FoxP3 and human leucocyte antigen D‐related (HLA‐DR) expression, while numbers of circulating T<sub>regs</sub> remained unchanged. The enhanced activation was sustained for at least 7 days after infusion, and the suppressive capacity of purified T<sub>regs</sub> was increased from 41 to 70% at day 7 after IVIg treatment. The activation status of T<sub>conv</sub> was not affected by IVIg. We conclude that high‐dose IVIg treatment activates T<sub>regs</sub> selectively and enhances their suppressive function in humans <italic>in vivo</italic>. This effect may be one of the mechanisms by which IVIg restores imbalanced immune homeostasis in patients with autoimmune and systemic inflammatory disorders.</p> </abstract>