FIGURE 4.

Activation pathways in pathogenic CD4⁺ T cells. Multiple signaling pathways contribute to the activation of pathogenic CD4⁺ T cells in giant cell arteritis. Antigen recognition by the T cell receptor triggers rapid division, differentiation and lineage commitment. CD28 receptor engagement co-stimulates, mediated through AKT phosphorylation and downstream activation of the mechanistic target of rapamycin complex 1 (mTORC1). Additional stimuli derive from metabolic signals. Glucose uptake is controlled through the expression of the glucose transporter 1 (GLUT1). Glycolytic breakdown generates pyruvate, which functions as a critical energy carrier for mitochondria, sustaining ATP production and the release of metabolic intermediates. Antigen-stimulated, metabolically active CD4⁺ T cells differentiate into effector cells secreting IFN-γ, IL-17, and IL-21 and sustain a vessel wall remodeling program resulting in wall vascularization and lumen-occlusive intimal hyperplasia.