Figure 5.

Abnormal T cell Activation in GCA. The intensity and duration of adaptive immunity depends on the availability of specific antigen, but also on a mixture of positive (co-stimulatory) and negative (co-inhibitory) signals, that modulate the T cell receptor activation cascade. Patients with GCA have abnormalities in the CD28 co-stimulatory pathway and in the co-inhibitory PD-1/PD-L1 pathway, resulting in sustained and unopposed activation of pathogenic T cells. Under physiologic conditions, CD28 on T cells recognizes CD80/86 on antigen-presenting cells (e.g. dendritic cells; DC), prolonging and intensifying T cell activation. Signaling through this pathway is intensified in GCA. Under physiologic conditions, PD-1 on T cells recognizes PD-L1 on antigen presenting cells (e.g. macrophages; Mac), resulting in dampening of T cell activation. In GCA, PD-L1 is expressed at very low levels, disrupting this negative signal, and boosting T cell effector functions.