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Figure 4: Proposed sequence of events leading to the development of chronic autoimmune diseases. In individuals with a genetic deficiency of CD8+ T cells (carried by “Autoimmune genes”) and with HLA class II genes predisposing to idiopathic dilated cardiomyopathy (HLA-DR4 [206]), primary biliary cirrhosis (HLA-DR8 [207]), and Crohn’s disease (HLA-DR7 [208]), primary EBV infection, particularly if delayed (Late), leads to the infection of autoreactive B cells, which accumulate in the target organ where they reactivate autoreactive T cells that orchestrate an autoimmune attack on the organ. For simplicity these depictions focus on the role of CD8+ T-cell deficiency, EBV infection and selected HLA alleles and do not include interactions with other genetic and environmental factors that may also contribute to the pathogenesis of autoimmune diseases.