Although expression of granzyme B by CD8+ cytotoxic T cells in tissues suggests a direct pathogenic role in the development of tissue damage, the ratio of CD8+ cytotoxic T cells to total number of T cells in the tissue section (defined by CD3 positivity on immunohistochemistry) was found to be similar in high-grade and low-grade ICI-induced myocarditis, suggesting that other factors may modulate the severity of disease [95]. The gene discussed is CD8A; the disease is myocarditis.