Anti-CD20 therapy corrects a CD8 regulatory T cell deficit in multiple sclerosis

To determine the effect of long-term anti-CD20 B-cell-depleting treatment on regulatory T cell immune subsets that are subnormal in untreated MS patients.

30 clinically stable MS patients, before and over 38 months of ocrelizumab treatment, were compared to 13 healthy controls, 29 therapy-naïve MS, 9 interferon-β-treated MS, 3 rituximab-treated MS, and 3 rituximab-treated patients with other autoimmune inflammatory diseases. CD8, CD28, CD4, and FOXP3 expression in peripheral blood mononuclear cells was quantitated with flow cytometry.

CD8⁺ CD28^- regulatory cells rose from one-third of healthy control levels before ocrelizumab treatment (2.68% vs 7.98%), normalized by 12 months (13.5%), and rose to 2.4-fold above healthy controls after 18 months of ocrelizumab therapy (19.0%). CD4⁺ FOXP3⁺ regulatory cells were lower in MS than in healthy controls (7.98%) and showed slight long-term decreases with ocrelizumab. CD8⁺ CD28^- and CD4⁺ FOXP3⁺ regulatory T cell percentages in IFN-β-treated MS patients were between those of untreated MS and healthy controls.

Long-term treatment with ocrelizumab markedly enriches CD8⁺ CD28^- regulatory T cells and corrects the low levels seen in MS before treatment, while slightly decreasing CD4⁺ FOXP3+ regulatory T cells. Homeostatic enrichment of regulatory CD8 T cells provides a mechanism, in addition to B cell depletion, for the benefits of anti-CD20 treatment in MS.