When helpers go above and beyond: characterization of cytotoxic CD4 + T cells in multiple sclerosis

Multiple sclerosis (MS) is the most common neurological disorder in young adults, and has a huge impact on day-to-day life of patients. MS often limits these persons in pursuing their dreams and ambitions regarding professional careers, starting a family, and participating in social activities. While today several treatment options for especially the early phase of MS exists, no cure is currently available. A specific type of immune cell, called T cell, is thought to be one of the cells responsible for development of MS and its progression in time. T cells can be divided into many subtypes with each its own function. While more and more information has been gathered on the role of T cells in MS, it is becoming clear that there is a need for new therapies that can very specifically eliminate the bad types of T cells and leave the good types of T cells intact. In this dissertation, I focus on the subset of CD4+ T cells that have cytotoxic properties (called CD4 CTL), meaning that these cells can directly kill other cells. There is some evidence in literature that CD4 CTL go to the brain of MS patients, where they can attack oligodendrocytes. These oligodendrocytesform a protective lining around our nerves, and death of these cells causes the characteristic symptoms of MS like numbness, fatigue, weakness, and loss of vision. In this work, CD4 CTL are studied in great detail to uncover specific features of these cells, which might be specifically targeted in new therapies. It is found that several types of CD4 CTL exist, with some types better equipped to cause damages than others. Additionally, CD4 CTL are shown to be able to leave the blood circulation and reach the brain of MS patients. Some evidence is presented that two markers in particular, called CRTAM and Eomes, might be responsible for this. Furthermore, CD4 CTL are found to be insensitive to Tregs, another type of T cells that normally keep other immune cells in check and prevent them from harmful overreacting. CD4 CTL themselves interact with other T cells to make these cells more capable of causing inflammation. Considering all this information together, this dissertation provides insights into how CD4 CTL have the potential to cause or worsen MS. Future research should be conducted to confirm that specific subtypes of CD4 CTL, to be recognized by markers like CRTAM, Eomes, and specific cytotoxic molecules, can be targeted with new therapies to limit disease progression of MS patients.

Jaar van publicatie:2023

Toegankelijkheid:Embargoed