How do CD8 T cells make it to the lungs to help in the fight against infection? Why don’t T cells remain longer in the lungs? How can science optimize that journey with vaccine additives?
When a virus like the flu first makes its way into the human body and prepares to launch an invasion, the cells of the lungs are often the first under attack. New findings from Emory University highlight a T cell receptor and its ligand that pull specific, infection-fighting T cells to the lungs. Harnessing the recruitment power of this receptor-ligand pair would be particularly useful when added to a vaccine, i.e. the annual influenza vaccine.
CD8, or cytotoxic, T cells are immune cells that target and destroy infected and cancerous cells. They are produced in the thymus and express a CD8 receptor (other T cells express CD4 receptors and function differently). The viral epitopes that CD8 T cells recognize when scanning for infected cells normally stay the same over time, unlike other components of viruses like influenza that keep vaccine scientists on their toes when tasked with the creation of an annual vaccine.
Emory University scientists found the CD8 T cell receptor CXCR6 and its ligand CXCL16 as necessary for CD8 T cells to reach lung tissue, a process that is particularly critical in cases of lung infection. Epithelial cells lining the airways leading to the lungs produce the ligand CXCL16. The CXCR6 receptor is found on the surface of CD8 T cells, and it streamlines CD8 T cell travel to the lungs.
The study conducted was done with a mouse model of disease, but researchers have also shown that the CXCR6 T cell receptor is also prevalent in CD8 T cell populations in human lungs. Likewise, the CXCL16 ligand is produced by airway epithelium in humans.
The receptor-ligand pair identified in this study joins other receptor-ligand pairs that pull T cells to various other tissues in the human body. But unlike the intestines and skin, lung tissue has been more difficult to investigate because of the sheer number of blood vessels stretching in and out of the lungs.
"If we can get long-lived T cells into the lungs of people that recognize conserved epitopes of influenza virus, they will get infected but have decreased symptoms or even be asymptomatic," explained co-first author Alex Wein, a MD/PhD student.