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Arch Neurol. 2008 Nov;65(11):1434-9. doi: 10.1001/archneur.65.11.1434.

Interferon beta-induced restoration of regulatory T-cell function in multiple sclerosis is prompted by an increase in newly generated naive regulatory T cells.

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  • 1Division of Molecular Neuroimmunology, Department of Neurology, University of Heidelberg, Heidelberg, Germany.

Abstract

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.

PMID:
19001161
[PubMed - indexed for MEDLINE]
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