T Cell Warriors: Mobilising the Anti-Viral Response to Combat Ageing Cells
As we are exposed to microbes throughout life, our immune system evolves and undergoes significant changes. Microbes can be harmful and cause infection, or live in harmony with us and form part of our “microbiome”. Our immune system faces the challenging battle to both defend against the “bad” microbes, and build tolerance to the “good” microbes.
A newborn baby’s immune system is less able to defend against these early life threats. To compensate for this diminished function, a mother passes antibody immunity through the umbilical cord during pregnancy.
Other key players of the immune system, T cells, have attracted considerable attention since the COVID-19 pandemic. At birth, the proportions of T cells are elevated, and a larger population are classified as “naive” due to their lack of exposure to microbes. Additionally, T cells from babies exhibit functional distinctions from adult T cells. Upon encountering bacteria, viruses, and fungi, the immune system learns to respond more rapidly. As part of this immunological memory, T cells more readily kill infected cells and make enhanced vaccine responses. However, in the elderly, immunity deteriorates leaving them vulnerable to infections and less able to respond to vaccines. Advanced age is associated with chronic low-grade inflammation, known as “inflammaging”, as well as age-related diseases such as cancer, neurodegeneration, and fibrosis. A contributing factor to such diseases is the accumulation of ageing cells, termed “senescent cells”, which stop dividing. Accordingly, senescent cells are promising therapeutic targets to treat age-related diseases.
Anti-viral T cell responses
T cells are grouped into “helper” T cells expressing the glycoprotein CD4 (CD4+ T cells), and “cytotoxic” T cells expressing the glycoprotein CD8 (CD8+ T cells). By recognising microbial components presented on cell surfaces, helper T cells provide support for antibody responses, while cytotoxic T cells produce molecules that directly kill infected cells. However, there is some overlap; for example, a population of CD4+ T cells express these killing molecules, known as “cytotoxic CD4+ T cells”.
Boosting the body’s anti-viral T cell response has long been known to be an effective strategy to protect against viral disease. This dates back to the historic immunological breakthrough, in 1796, when Edward Jenner expanded on the work of Lady Mary Wortley Montagu and Benjamin Jesty by inventing the smallpox vaccine. Eventually, the vaccine led to the eradication of smallpox, and to a host of successful vaccines such as rabies, influenza, polio, and yellow fever. Could anti-viral T cell responses be useful in the fight against other diseases?
Weapons against ageing cells
Recently, added benefits of the anti-viral T cell response have been identified. The Demehri Lab at Massachusetts General Hospital have discovered that the anti-viral T cell response to human cytomegalovirus (HCMV), a virus that infects most of the human population, reduces ageing cells in the skin. In older skin, increased proportions of cytotoxic CD4+ T cells were present. Greater proportions of these cells were associated with fewer ageing cells, suggesting that the T cells had a role to play. Could the T cells be fighting ageing cells?
Remarkably, the researchers went on to show that the T cells recognised HCMV antigen on the cell surface and engaged their anti-viral response to eliminate the ageing cells. Therefore, the anti-viral T cell response can act as a weapon against both viruses and ageing cells.
Future outlook
These findings reveal new functions of T cells and highlight a beneficial role of the immune-microbe axis in healthy ageing. Excitingly, boosting the anti-viral T cell response may eliminate ageing cells and help treat age-related diseases. We are already starting to see patent applications being filed for vaccines against senescent cells. These findings also open up new avenues in cosmetic dermatology and may lead to new treatments in anti-ageing formulas.
J A Kemp has expertise in handling patents relating to immunology. For more information see our Immunology and Immunotherapy, and Vaccines and Virology, specialisms.