Interferon Beta–Induced Restoration of Regulatory T-Cell Function in Multiple Sclerosis Is Prompted by an Increase in Newly Generated Naive Regulatory T Cells
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.
Cited By (2)
- T cells in multiple sclerosis and experimental autoimmune encephalomyelitisClinical & Experimental Immunology · 2010
- Effect of IFN-ß therapy on the frequency and function of CD4+CD25+ regulatory T cells and Foxp3 gene expression in relapsing–remitting multiple sclerosis (RRMS): A preliminary studyJournal of Neuroimmunology · 2010
References (5)
- Compromised CD4+ CD25high regulatory T‐cell function in patients with relapsing‐remitting multiple sclerosis is correlated with a reduced frequency of FOXP3‐positive cells and reduced FOXP3 expression at the single‐cell levelImmunology · 2008
- CD4+CD25bright Regulatory T Cells Actively Regulate Inflammation in the Joints of Patients with the Remitting Form of Juvenile Idiopathic ArthritisThe Journal of Immunology · 2004
- Prevalence of Newly Generated Naive Regulatory T Cells (Treg) Is Critical for Treg Suppressive Function and Determines Treg Dysfunction in Multiple SclerosisThe Journal of Immunology · 2007
- Interferon beta-1a therapy enhances CD4+ regulatory T-cell function: an ex vivo and in vitro longitudinal study in relapsing-remitting multiple sclerosis
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