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Laatste wijziging: 24 januari 2022
A role for immunosenescence and CD4+CD28- T-cells in patients with multiple sclerosis
Principal Investigator: Prof. Dr. Niels Hellings, Researcher: Marjan Vanheusden
In 20% of the people with multiple sclerosis (MS), an autoimmune disease of the central nerve system, a certain subtype of T cells: CD4+CD28 T-cells, is found. These cells are an important feature of the aging of the immune system. The cause of the occurrence and expansion of these cells and their role in the MS pathology is unknown. It is thought that cytomegalovirus (CMV) plays a role in the onset and optionally in the expansion of CD4+CD28+ T-cells, namely via chronic antigen presentation. Furthermore, it is suggested that this CD28+CD4 T-cell population may contribute to damage to the central nervous system.
This study will examine whether MS patients possessing these CD4+CD28 T-cells or exhibiting immune-aging, have a worse disease progression compared to patients without these cells.
First, we will investigate whether there is a difference between MS patients with and without CD28+CD4 T-cells at clinical, genetic and immunological level. Clinical parameters (EDSS, MSSS, type, number of relapses, ...) and biomarkers present in the cerebrospinal fluid will be determined, to investigate whether the burden and the clinical course of disease is worse in MS patients carrying these cells. Genetic factors, such as "single nucleotide polymorphisms" that are associated with MS and cytomegalovirus, will be studied in order to find out if they could lead to the expansion of CD28+CD4 T-cells. Further immunological differences will be examined by studying the cytokine profile between the two groups of patients and by screening of the immune cells, such as Th17 and Tregs, which are disrupted in MS. Finally, the impact and mechanisms of CMV infection on the expansion of CD4+CD28+ T-cells will be studied.
This research will provide more clarity about the pathogenesis of MS and will contribute to the development of a more targeted treatment of MS patients.
Peeters LM, Vanheusden M, Somers V, Van Wijmeersch B, Stinissen P, Broux B, Hellings N. Cytotoxic CD4+ T Cells Drive Multiple Sclerosis Progression. Front Immunol. 2017;8:1160.
Vanheusden M, Broux B, Welten SP, Peeters LM, Panagioti E, Van Wijmeersch B, Somers V, Stinissen P, Arens R, Hellings N. Cytomegalovirus infection exacerbates autoimmune mediated neuroinflammation. Sci Rep. 2017;7(1):663.
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