期刊
JOURNAL OF AUTOIMMUNITY
卷 102, 期 -, 页码 38-49出版社
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.jaut.2019.04.013
关键词
Autoimmunity; Multiple sclerosis; Myelin oligodendrocyte glycoprotein; Autoantigen; T-cell
类别
资金
- CBD solutions
- Neuroforbundet
- Swedish Research Council [2017-00777]
- Swedish Brain Foundation
- Margareta of Ugglas Foundation
- Stratneuro
- DFG [SFB TR128]
- Swedish Research Council [2017-00777] Funding Source: Swedish Research Council
Autoreactive CD4(+) T-cells are believed to be a main driver of multiple sclerosis (MS). Myelin oligodendrocyte glycoprotein (MOG) is considered an autoantigen, yet doubted in recent years. The reason is in part due to low frequency and titers of MOG autoantibodies and the challenge to detect MOG-specific T-cells. In this study we aimed to analyze T-cell reactivity and frequency utilizing a novel method for detection of antigen-specific T-cells with bead-bound MOG as stimulant. Peripheral blood mononuclear cells (PBMCs) from natalizumab treated persons with MS (n = 52) and healthy controls (HCs) (n = 24) were analyzed by IFN gamma/IL-22/IL-17A FluoroSpot. A higher number of IFN gamma (P = 0.001), IL-22 (P = 0.003), IL-17A (P < 0.0001) as well as double and triple cytokine producing MOG-specific T-cells were detected in persons with MS compared to HCs. Of the patients, 46.2-59.6% displayed MOG-reactivity. Depletion of CD4(+) T-cells or monocytes or blocking HLA-DR completely eliminated the MOG specific response. Anti-MOG antibodies did not correlate with T-cell MOG-responses. In conclusion, we present a sensitive method to detect circulating autoreactive CD4(+) T-cells producing IFN gamma, IL-22 or IL-17A using MOG as a model antigen. Further, we demonstrate that MOG-specific T-cells are present in approximately half of persons with MS.
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