Combining “loss of function” using CD8 cell-depleting treatment with anti-CD8 mAb and “gain of function” strategy based on CD8+ T cell supplementation in Rag1−/− mice, we showed that CD8+ T cells promoted deleterious post-ischemic cardiac remodeling at early (day 21) and late stages (day 56) in a murine model of permanent coronary occlusion, as well as in a pig model of coronary ischemia-reperfusion. Here, CD8A is linked to ischemia.