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 (Treg) 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+ Treg 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+ Treg. 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 One subject was withdrawn owing to an adverse effect.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+ Treg was observed during treatment. Anti-CD25 antibody treatment led to evidence of impaired in vivo Treg proliferation and impaired ex vivo Treg suppression. Inflammatory MS activity was substantially reduced with treatment despite reduction of circulating Treg, and there was no correlation between changes in the frequency of Treg 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 Treg 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+ Treg.

Root growth and metal uptake in four grasses grown on zinc-contaminated soils.

Depth and area of rooting are important to long-term survival of plants on metal-contaminated, steep-slope soils. We evaluated shoot and root growth and metal uptake of four cool-season grasses grown on a high-Zn soil in a greenhouse. A mixture of biosolids, fly ash, and burnt lime was placed either directly over a Zn-contaminated soil or over a clean, fine-grained topsoil and then the Zn-contaminated soil; the control was the clean topsoil. The grasses were 'Reliant' hard fescue (Festuca brevipila R. Tracey), 'Oahe' intermediate wheatgrass [Elytrigia intermedia (Host) Nevski subsp. intermedia], 'Ruebens' Canada bluegrass (Poa compressa L.), and 'K-31' tall fescue (Festuca arundinacea Schreb.). Root growth in the clean soil and biosolids corresponded to the characteristic rooting ability of each species, while rooting into the Zn-contaminated soil was related to the species' tolerance to Zn. While wheatgrass and tall fescue had the strongest root growth in the surface layers (0-5 cm) of clean soil or biosolids, wheatgrass roots were at least two times more dense than those of the other grasses in the second layer (5-27 cm) of Zn-contaminated soil. When grown over Zn-contaminated soil in the second layer, hard fescue (with 422 mg/kg Zn) was the only species not to have phytotoxic levels of Zn in shoots; tall fescue had the highest Zn uptake (1553 mg/kg). Thus, the best long-term survivors in high-Zn soils should be wheatgrass, due to its ability to root deeply into Zn-contaminated soils, and hard fescue, with its ability to effectively exclude toxic Zn uptake.