Multiple Sclerosis – a Role of Regulatory T Cells in the Pathogenesis and Biological Treatment of the Disease
Authors:
M. Buc
Authors‘ workplace:
Imunologický ústav LF UK, Bratislava
Published in:
Cesk Slov Neurol N 2013; 76/109(3): 293-299
Category:
Review Article
Overview
Every biological system has its executive as well as control mechanisms that, by the means of feed back, maintain homeostasis within the organism. Regulatory B cells (Breg) and especially regulatory T cells (Treg) are of paramount importance in preventing auto‑ aggressive (allergic and autoimmune) processes. Multiple sclerosis (MS) is an autoimmune disease driven by proinflammatory activities of various cell types led by TH1 and TH17 cells. Recently, it has been established that the over‑activity of the involved cells is enabled by insufficient activity of regulatory T cells. It is, therefore, natural that, in MS, therapy aims to re‑establish their physiological function. IFN‑β and glatiramer acetate, first line biological agents, are able to do so. The second line agents, natalizumab and FTY720, influence the activity of Treg cells in various ways – natalizumab does not affect T cells in any way, while FTY720 supports both, their proliferation and activity. It seems that it is an insufficient immunosuppressive activity after suspension of the 720 (FTY720) treatment that results in a development of the IRIS. With respect to the role of regulatory T cells in the development and therapy of MS it is worth mentioning that they can be induced and expanded in vitro and subsequently re‑introduced to the patient. Recently, monoclonal antibodies rituximab, alemtuzumab and daclizumab have entered clinical tests as the treatments of MS. Their mechanisms of action are different. Rituximab down‑ regulates antigen‑ presentation function of B cells, alemtuzumab profoundly depletes T cells, including auto‑ reactive lines, and daclizumab induces NK cells that enter the itrathecal compartment and kill autoreactive T cells. The paper also discusses the support that laboratory immunology has to offer to physicians in terms of the diagnosis and biological treatment decision making.
Key words:
glatiramer acetate – interferon b –monoclonal antibodies – regulatory T cells – multiple sclerosis – TH1 cells – TH17 cells
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Paediatric neurology Neurosurgery NeurologyArticle was published in
Czech and Slovak Neurology and Neurosurgery
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