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Mirjam Korporal, MD; Juergen Haas, PhD; Bettina Balint; Benedikt Fritzsching, MD; Alexander Schwarz, MD; Sigrid Moeller, MD; Brigitte Fritz; Elisabeth Suri-Payer, PhD; Brigitte Wildemann, MD

Arch Neurol. 2008;65(11):1434-1439.

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.

Author Affiliations: Division of Molecular Neuroimmunology, Department of Neurology (Drs Korporal, Haas, Schwarz, Moeller, and Wildemann and Mss Balint and Fritz), and Division of Neonatology, Children's Hospital (Dr Fritzsching), University of Heidelberg, and Division of Immunogenetics/Tumor Immunology Program, German Cancer Research Centre (Dr Suri-Payer), Heidelberg, Germany.

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