The dysregulated immune response in PD-1−/− mice was secondary to the clonal expansion of autoreactive cytotoxic effector CD8+ T cells that resulted in increased cardiac hypertrophy, persistent mild LV dysfunction, and increased mortality, thereby revealing a previously unappreciated role for the role of co-inhibitory immune checkpoints in restraining CD8+ T responses in the heart following repetitive tissue injury. The gene discussed is CD8A; the disease is cardiac hypertrophy.