Research findings show three failures in this immune privilege in GCA: Patients have increases in CD4 T cells, a leakiness in the aorta’s access portal that would normally keep out inflammatory cells and defective immune checkpoints.
In their lymphoid tissues, GCA patients have low levels of CD8 T-regulatory cells with a surface marker called NADPH oxidase. Normally, macrophages use this oxidase to form exosomes that infiltrate CD4 cells and stop their function, killing bacteria. Immune dysregulation in GCA causes these patients to have more active CD4 T cells, she said.1
Inflammatory cells enter the aorta through the vasa vasoral networks of the adventitia. Using biopsy data, she and her colleagues found two signals of gene expression in the inflamed arteries of GCA patients: Jagged-1 and NOTCH-1.2 Jagged-1 is the ligand and NOTCH-1 is the receptor, she said. Through high-resolution imaging, they found that Jagged-1 is expressed on the vasa vasorum structures, and the ligand is expressed on the cell surface. With flow cytometry, they also found that the receptor sits on the circulating CD4 T cells of GCA patients.