T Cells
T cells are a type of immune cell that play a crucial role in the immune system's response to various challenges, including infections, diseases, and tissue healing. They are particularly relevant in the context of immunosenescence, which is the age-related decline of the immune system.
Immunosenescence and T Cells
Immunosenescence is characterised by a diminished diversity and response capability of T cells. This decline impacts the body's ability to heal tissues and increases susceptibility to infections. The mechanisms driving immunosenescence include:
- Thymic Involution: This process reduces the immune system's ability to respond to new antigens by decreasing thymopoiesis and shifting towards memory T cells.
- Inflammaging: Chronic systemic inflammation further impairs immune function.
- Cellular Changes: Metabolic adaptations, haematopoietic modifications, and altered intercellular communication disrupt immune coordination.
- Stem Cell Exhaustion: This hinders tissue regeneration and immune cell development.
- Genomic Instability: Accumulation of DNA damage and somatic mutations affect immune cell function.
- Epigenetic Alterations: Changes in gene expression patterns impact immune cell development and function.
- Gut Microbiome Changes: The gut microbiome undergoes significant changes with age, characterised by a decrease in beneficial bacteria and an increase in pro-inflammatory species.
- Mitochondrial Dysfunction: Impaired mitochondrial function affects immune cell activation and proliferation.
- Circadian Rhythm Disruptions: Disturbances to daily cycles impact immune function.
T Cell Changes in Immunosenescence
Immunosenescence results in the accumulation and clonal expansion of memory and effector T cells, the reduction/exhaustion of naive T cells, and the shrinkage of the T cell repertoire. This can be viewed as a global reduction of the "immunological space".
Aryl Hydrocarbon Receptor (AHR) and T Cells
The Aryl Hydrocarbon Receptor (AHR) is a receptor protein found within cells that plays a critical role in immune responses and tissue healing. Insufficient AHR activation can cause an immune system imbalance, leading to diseases. Restoring AHR activity has shown promise in aiding wound healing and treating autoimmune diseases, particularly systemic lupus erythematosus (lupus).
In lupus, insufficient activation of AHR results in too many disease-promoting immune cells, called T peripheral helper cells, that promote the production of disease-causing autoantibodies. Returning AHR-activating molecules to blood samples from lupus patients seemed to reprogram these lupus-causing cells into a cell called a Th22 cell that may promote wound healing from the damage caused by this autoimmune disease.
Conclusion
Understanding the mechanisms of immunosenescence and the role of T cells is crucial for developing interventions to enhance immunological function in the elderly population. Researchers are investigating interventions to target senescent cells and slow ageing, such as senolytics, epigenetic reprogramming, and immune-mediated clearance. The field of geroscience focuses on understanding the complex mechanisms of immunosenescence at a molecular level to develop strategies to prevent age-related illnesses.