T cells are one of the three main types of a group of white blood cells known as lymphocytes. The other types include B cells and Natural killer NK cells. Unlike the B and NK cells, these T cells express protein receptors on their membrane surface called T cell receptors. Recognition of antigenic substances by these receptors triggers an immune response from the T cells aimed at protecting the body from the detected foreign invader. Ironically, this protective mechanism also has the propensity to drive the formation of atherosclerotic plaques in the arterial walls which is the leading cause of the incurable cardiovascular disease known as atherosclerosis. This disease has remained incurable mainly because its culprit cells have been able to remain unidentified.
However, a study published recently in Nature Cardiovascular Research was able to pinpoint these culprit T cells. The study conducted by researchers at La Jolla Institute for Immunology (LJI), San Diego, California, in collaboration with scientists at Albert Einstein College of Medicine solves the major puzzle behind the treatment of atherosclerosis and ultimately, cardiovascular disease.
Identifying the culprit T cells involved in the formation of atherosclerotic plaque
In the study, researchers obtained blood samples from eight women in a diverse cohort of women in their 50s and 60s. These women were volunteers in the NIH-funded Women’s Interagency HIV Study.
Using single-cell RNA sequencing and T cell receptor sequencing, the team then went further to carefully analyze more than 12,000 T cells in the blood samples obtained from the volunteers. They observed that 110 cells out of the vast number of T cells were distinct. They also discovered that these distinct cells were capable of targeting a protein known as apolipoprotein B (APOB).
Further analyses revealed that the cells closely resembled a type of T cells known as regulatory T cells (Treg), which normally exert a regulatory role over the inflammatory process. Surprisingly, the researchers discovered that although these culprit cells resembled the normal Treg cells, they were not totally similar in identity as they had acquired new identities with the progression of the heart disease.
They then theorized that T cells that target the APOB protein may contribute to inflammation and therefore drive the progression of atherosclerosis. However, they also realized that once activated, the APOB reactive T cells became aggressive. Results from follow-up experiments conducted in mice strongly validated this theory. In these animal experiments, a phenomenon known as T cell expansion which resulted in an increased number of APOB reactive T cells occurred in the bloodstream which in turn worsened the disease in the animals.
APOB is a component of LDL or bad cholesterol, and recognition of this compound by T cells drives the atherosclerotic plaque formation. These plaques block the blood vessel resulting in ischemic diseases like stroke and cardiovascular disease. Recognition of these APOB-reactive cells gives insight into the development of vaccines targeted at suppressing the overt activity of these cells and thus reducing the incidence of cardiovascular heart disease.
This study brings into the limelight the culprit T cells involved in atherosclerosis a leading cause of cardiovascular diseases thus bringing researchers a step closer to understanding the pathogenesis of these diseases and developing an effective and absolute cure for them.