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The role of regulatory T cells in rheumatoid arthritis

The role of regulatory T cells in rheumatoid arthritis

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An essay for the 2011 Undergraduate Awards Competition by Angela Mc Ardle. Originally submitted for Biochemistry with Immunology at Trinity College, Dublin, with lecturer Jean Fletcher in the category of Medical Sciences
An essay for the 2011 Undergraduate Awards Competition by Angela Mc Ardle. Originally submitted for Biochemistry with Immunology at Trinity College, Dublin, with lecturer Jean Fletcher in the category of Medical Sciences

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Published by: Undergraduate Awards on Aug 29, 2012
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03/29/2014

 
 
The role of regulatory T cells in rheumatoid arthritis
 
 
Abstract:
Rheumatoid arthritis (RA) is a CD4
+
T cell mediated autoimmune disease which hasdevastating effects. The main features of this disease are the inflammation of the synoviumand the damage to joint structures such as cartilage and bone. There is evidence thatregulatory T cells (Tregs) have a vital role in the prevention of autoimmune disease and arepotent suppressors of CD4
+
T cells. Studies investigating their role in RA provide conflictingevidence. In some studies Tregs were found to prevent disease severity while in others theywere unable to modulate the disease due to defects in their function. Studies investigatingTregs isolated from patients and mouse models of RA have highlighted the benefits of enhancing Treg function and numbers, suggesting these could be important therapeuticsteps in the treatment of RA.
Introduction
The body’s immune system protects an individual from harmful infectious pathogens. It
usesa number of mechanisms that allow it to recognize and respond to foreign antigens whileavoiding recognition and response to self antigens expressed on all body cells. The ability todistinguish between the two is vitally important. Failure to do so results in autoimmunedisease,
where the immune system attacks the body’s own cells re
sulting in tissue andorgan damage [1]. Such diseases affect approximately 2-5% of the population [2]. Althoughthe exact origin of autoimmune disease is unknown, it is thought that a breakdown in self distinguishing mechanisms as well as genetic and environmental factors (such as viralinfection) trigger the onset of such diseases. Autoimmune diseases may be organ specific,affecting only certain organs or systemic, affecting many organs of the body [2, 3].RA is a chronic systemic autoimmune disease. It is one of the most common autoimmunediseases effecting 1% of the population, women are more commonly affected than men [4-6]. The main feature of RA is the inflammation of the synovium (the thin lining of joints) asillustrated in Fig. 1. [7]. RA is most prevalent in the small diarthridal joints of the hands andfeet while systemic effects can be seen in the lungs as fibrosis and in the circulatory systemas atherosclerosis [7, 8]. The synovium has two layers, an inner and an outer layer. Itbecomes filled with abnormally high numbers of lymphocytes, neutrophils, macrophagesand synovium like fibroblast cells which mount an attack on the joint and releaseproinflammatory cytokines. The inner lining of the joint becomes enlarged due toabnormally high numbers of macrophages and synovium like fibroblasts. The fibroblast cellscome together and form a pannus which covers over the cartilage and mediates bothcartilage and bone destruction by degradative enzymes [7, 9]. Patients with RA suffer severe
 
pain and loss of function. It is common for people with RA to leave their place of occupationwithin two years of suffering from the disease and thus lose their contribution to society. Inaddition to individual suffering, RA creates an economical burden on society costing millionsof pounds on health care and sick leave (UK data) [7-9]. As the disease progress into achronic state people suffer permanent joint damage and become completely disabled.Severe RA often results in death by heart attack or strokes that occur due to atherosclerosisin the circulatory system [8].It is not yet known what causes RA [2]. Studies have shown genetic factors are involved inprovoking autoimmune diseases and this is true for RA [3]. MHC molecules which present toT lymphocytes are the most common genetic instigators of autoimmune disease. In humansthe HLA genes encode for proteins that form MHC molecules. These genes are highlypolymorphic and a defective polymorphism could give rise to an MHC molecule that isincapable of presenting antigen in an appropriate manner [2, 10]. The consequence of thismay be severe during the positive and negative selection of developing CD4
+
T cells in thethymus. Incorrect presentation may then lead to autoreactive CD4
+
T cells escaping deletionand entering the periphery. HLA-DR genes encode for MHC class II molecules. In RA patientsFig.1:
A healthy vs.Arthritic joint.Inflammation of thesynovium, a reductionin synovial fluid,cartilage and bonedamage is evident inthe rheumatoidarthritis joint.
 

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