APOE and atherosclerosis: However, ApoE − /− Cd4 − /− mice had significantly increased early lesions, and early depletion of CD4 + T cells accelerated atherosclerosis, indicating that early CD4 + T cell-mediated responses are largely protective against the disease.6,463–465 In addition, CD4 + T cells activate macrophages and induce smooth muscle cell apoptosis by secreting Th1 cytokines and Th2 cytokines.461 Tregs are also crucial for myocardial repair.