Regulatory T cells are reduced during anti-CD25 antibody treatment of multiple sclerosis

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 Treg 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 One subject was withdrawn owing to an adverse effect.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 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 compart- mental differences in the capacity to maintain tolerance in the setting of reduced CD4⁺CD25⁺ T_reg.