Canadian study reveals subgroup of T cells which target oligodendrocytes in MS
Background: Immune cells and targets
It is believed that multiple sclerosis disease is prompted by a series of immunological events. However, the mechanism by which immune cells enter the central nervous system (CNS) and cause tissue damage remains to be defined. A group of lymphocytes known as CD4 T cells which, under normal conditions, recognize and clear pathogens has been demonstrated to have lethal effects on oligodendrocytes in MS. These cells are marked by a surface protein called CD56, which can also be found on NK cells and has been associated with cell injury.
This evidence provides important insight into the events which lead to myelin damage and onset of MS. However further research has shown that CD56 is not the only molecule involved in this response, and that other NK cell-associated proteins, particularly of the NKG2C family, may also play a part.
MS Society of Canada Operating Grant recipient Dr. Nathalie Arbour and Master of Science studentship awardee Fatma Zaguia, both from University of Montreal, have collaborated with leading Canadian as well as international scientists on a study which aims to identify specific cell proteins on CD4 T cells that may have a role in MS. Their research was recently highlighted in In This Issue - a segment of the Journal of Immunology which features articles of advanced scientific merit.
The study looked at levels of different cell surface proteins on CD4 T cells that may be contributing to immune-mediated oligodendrocyte death. They achieved this by collecting blood from patients with MS, and conducted a series of cell-based experiments to determine whether molecules such as NKG2C are associated with the toxic activity of CD4 T cells.
What they found:
Results of the study demonstrated that CD4 T cells which bear NKG2C/CD56 surface molecules are harmful to oligodendrocytes. This outcome was not observed for other NK-related proteins, which highlights the importance of NKG2C in MS disease. Researchers also discovered that NKG2C can bind to specific molecules on oligodendrocytes, which further supports the notion that oligodendrocytes are a primary target of this auto-reactive CD4 T cell subgroup. To examine the specific role of NKG2C in MS, the researchers tested and compared levels in blood taken from untreated MS patients and healthy controls. The results revealed that CD4 T cells with NKG2C are more abundant in MS patients compared with healthy controls.
This study presents a novel mechanism wherein a specific subset of CD4 T cells in MS patients could identify and kill oligodendrocytes. The mechanism has been shown to be controlled by CD4 T cells which carry a specific cell marker that is in greater abundance in the blood of patients with MS versus healthy controls. These cells produce high levels of agents which are damaging to cells, suggesting a pathogenic role in MS. Current immunoregulatory therapies for MS target a broad range of cells, which often leads to adverse effects on the immune system and increased risk of infection. Identifying specific targets, such as NKG2C in harmful CD4 T cells, can help to minimize this response.
Zaguia et al. Cytotoxic NKG2C+ CD4 T Cells Target Oligodendrocytes in Multiple Sclerosis. The Journal of Immunology 2013 Mar 15;190(6):2510-8