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Unsong Oh, MD; Gregg Blevins, MD; Caitlin Griffith; Nancy Richert, MD, PhD; Dragan Maric, PhD; C. Richard Lee, MD, PhD; Henry McFarland, MD; Steven Jacobson, PhD

Arch Neurol. 2009;66(4):471-479.

Objective  Maintenance therapy with anti-CD25 antibody has emerged as a potentially useful treatment for multiple sclerosis (MS). Constitutive CD25 expression on CD4⁺CD25⁺ regulatory T cells (T_reg) suggests that anti-CD25 antibody treatment may potentially target a subset of T cells that exhibit immune suppressive properties. We examined changes to CD4⁺CD25⁺ T_reg in patients with MS receiving maintenance anti-CD25 monoclonal antibody treatment to determine the effect of treatment on T_reg and, consequently, on immunological tolerance.

Design  Peripheral blood and cerebrospinal fluid samples obtained from a before-and-after trial of anti-CD25 antibody monotherapy were examined to compare baseline and treatment differences in CD4⁺CD25⁺ T_reg.

Subjects  A total of 15 subjects with MS. One subject was withdrawn owing to an adverse effect.

Results  Sustained reduction of the frequency of CD4⁺CD25⁺ T_reg was observed during treatment. Anti-CD25 antibody treatment led to evidence of impaired in vivo T_reg proliferation and impaired ex vivo T_reg suppression. Inflammatory MS activity was substantially reduced with treatment despite reduction of circulating T_reg, and there was no correlation between changes in the frequency of T_reg and changes in brain inflammatory activity. However, new-onset inflammatory disease, notably dermatitis, was also observed in a number of subjects during treatment.

Conclusion  The reduction in T_reg did not negatively affect maintenance of central nervous system tolerance during anti-CD25 antibody treatment. The incidence of new-onset inflammatory disease outside of the central nervous system in a subset of patients, however, warrants further studies to examine the possibility of compartmental differences in the capacity to maintain tolerance in the setting of reduced CD4⁺CD25⁺ T_reg.

Author Affiliations: Neuroimmunology Branch, National Institute of Neurological Diseases and Stroke (NINDS) (Drs Oh, Richert, McFarland, and Jacobson), NINDS FACS (fluorescence-activated cell sorter) facility (Dr Maric), and Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland (Dr Lee); University of Alberta Medicine and Dentistry, Edmonton, Canada (Dr Blevins); and Grove City College, Grove City, Pennsylvania (Ms Griffith).

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