Patients treated with high‐dose intravenous immunoglobulin show selective activation of regulatory T cells

Summary Intravenous immunoglobulin ( IVI g) is used to treat autoimmune and systemic inflammatory diseases caused by derailment of humoral and cellular immunity. In this study we investigated whether IVI g treatment can modulate regulatory T cells ( T regs ) in humans in vivo . Blood was collected from IVI g‐treated patients with immunodeficiency or autoimmune disease who were treated with low‐dose ( n  = 12) or high‐dose ( n  = 15) IVI g before, immediately after and at 7 days after treatment. Percentages and activation status of circulating CD 4 + CD 25 + forkhead box protein 3 ( FoxP 3 + ) T regs and of conventional CD 4 + FoxP 3 − T ‐helper cells ( T conv ) were measured. The suppressive capacity of T regs purified from blood collected at the time‐points indicated was determined in an ex‐vivo assay. High‐dose, but not low‐dose, IVI g treatment enhanced the activation status of circulating T regs , as shown by increased FoxP 3 and human leucocyte antigen D‐related ( HLA ‐ DR) expression, while numbers of circulating T regs remained unchanged. The enhanced activation was sustained for at least 7 days after infusion, and the suppressive capacity of purified T regs was increased from 41 to 70% at day 7 after IVI g treatment. The activation status of T conv was not affected by IVI g. We conclude that high‐dose IVI g treatment activates T regs selectively and enhances their suppressive function in humans in vivo . This effect may be one of the mechanisms by which IVI g restores imbalanced immune homeostasis in patients with autoimmune and systemic inflammatory disorders.