Figure 6.

Pathogenic role of T cells in GCA. The shift from protective to pathogenic immunity in GCA involves multiple processes. Four major abnormalities have been molecularly defined (1). In GCA patients, CD4+ T cells aberrantly express NOTCH1, which facilitates T cell-endothelial communication, tissue entry and uncontrolled T cell expansion (2). Excess CD28-dependent signaling imprints a metabolic signature that sustains pro-inflammatory T cells (3). Such T cells supply a multitude of effector cytokine to stimulate macrophages and vascular cells (4). A critical feature of disease-promoting CD4⁺ T cells is the ability to establish tissue residency in the vessel wall. Tissue-resident memory CD4⁺ T cells render the lesion autonomous and ensure chronicity of disease.