Figure 2.

Infection of the thymus by CV-B4 can induce tolerance to the virus, leading to persistent infection of TECs, which play a crucial role in programming central immune self-tolerance. This infection causes severe thymic dysfunction and inhibits the expression of the gene encoding Igf2. Furthermore, it prevents the differentiation and maturation of lymphocytes, interfering with the intrathymic programming of central immunological self-tolerance, resulting in the breakdown of self-tolerance for the β-cells of the pancreatic islets. This leads to the production of self-reactive cytotoxic CD8+ T cells against insulin-producing β-cells, promoting their destruction. This same virus can also infect the spleen, causing the lysis of β-cells resulting in the release of autoantigens, leading to increased bystander activation of cytotoxic CD8+ T cells auto-reactive against β-cells, creating a positive feedback of an autoimmune process that can lead to T1DM. CV-B4, Coxsackievirus B4; TEC, thymic epithelial cell; Igf2, Insulin-like growth factor-2; T1DM, type 1 diabetes mellitus.