Interferon Beta–Induced Restoration of Regulatory T-Cell Function in Multiple Sclerosis Is Prompted by an Increase in Newly Generated Naive Regulatory T Cells

Background Naturally occurring regulatory T (T reg ) cells are functionally impaired in patients with relapsing-remitting multiple sclerosis. We recently showed that prevalences of newly generated CD31-coexpressing naive T reg cells (recent thymic emigrant–T reg cells) are critical for suppressive function of circulating T reg cells, and a shift in the homeostatic composition of T reg -cell subsets related to a reduced de novo generation of recent thymic emigrant–T reg cells may contribute to the multiple sclerosis (MS)–related T reg -cell dysfunction. Interferon beta, an immunomodulatory agent with established efficacy in MS, lowers relapse rates and slows disease progression. Emerging evidence suggests that T reg -cell suppressive capacity may increase in patients with MS undergoing treatment with interferon beta, although the mechanisms mediating this effect are uncertain. Objective To evaluate the effect of interferon beta treatment on the suppressive activity and the homeostasis of circulating T reg cells in patients with MS. Participants Twenty patients with relapsing-remitting MS and 18 healthy control subjects. Interventions Administration of interferon beta. Main Outcome Measures Effect of interferon beta on T reg -cell homeostasis and suppressive capacity. Results Suppressive capacities of T reg cells were consistently upregulated at 3 and 6 months after treatment with interferon beta. The restoration of T reg -cell function was paralleled by increased naive recent thymic emigrant–T reg cells and a coincidental reduction in memory T reg cells. Conclusion The increase in T reg -cell inhibitory capacity mediated by interferon beta treatment can be explained by its effect on the homeostatic balance within the T reg cell compartment.