Fig. 1.

Model for adaptive immune system involvement. A: chronic inflammatory conditions, immunological aging, and mechanical stimuli promote cell death and cytokine secretion by aortic valve interstitial cells (green) and antigen-presenting cells (APCs; blue), leading to activation of local APCs. B: APCs follow the lymphatic drainage to lymph nodes, where they prime and activate antigen-specific cytotoxic T lymphocytes and T helper cells (red and yellow, respectively) against valvular antigens. C: activated T cells enter the circulation and are recruited to the valve by local chemokine expression from both APCs and fibroblasts. D: T cells that have entered the valve recognize local antigens and release inflammatory cytokines, recruiting further immune cells and leading to increased myofibroblast transition of aortic valve interstitial cells.