Anti-CD20 therapy corrects a CD8 regulatory T cell deficit in multiple sclerosis
| Autor: | Timothy W Houston, Anthony T. Reder, Quentin Howlett-Prieto, Xuan Feng, Kevin J Kramer, John F Kramer |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
0303 health sciences
Multiple Sclerosis Regulatory T cell business.industry Multiple sclerosis CD8-Positive T-Lymphocytes Cd8 treg medicine.disease T-Lymphocytes Regulatory 03 medical and health sciences 0302 clinical medicine medicine.anatomical_structure Immune system Neurology T-Lymphocyte Subsets Immunology medicine Leukocytes Mononuclear Humans Neurology (clinical) Anti cd20 business 030217 neurology & neurosurgery CD8 030304 developmental biology |
| Zdroj: | Multiple sclerosis (Houndmills, Basingstoke, England). 27(14) |
| ISSN: | 1477-0970 |
| Popis: | Objective: 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. Methods: 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. Results: 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. Interpretation: 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|