title: [Role of viral infections in the pathogenesis of type 1 diabetes].
abstract: The precise role of viral infections in the pathogenesis of type 1 diabetes is still the subject of an important discussion. Coxsackievirus B4 (CVB4) is the virus the most implicated by a series of epidemiological studies. Pathogenic mechanisms underlying such a relationship implicate a molecular mimicry between CVB4 sequences and beta-cell autoantigens, but mainly a persistent CVB4 infection of pancreatic beta cells followed by a release of sequestered beta antigens and a "bystander" activation of autoreactive T cells. The demonstration of intrathymic expression of antigens specific of peripheral tissues has opened a novel research perspective. We have shown that CVB4 is able to infect in a persistent and producive manner human thymic epithelial cell cultures and human fetal thymic lobes in organotypic cultures. This infection induces an important thymic dysfunction characterized by a severe depletion of thymocytes (thymic T cells) and an up-regulated expression by thymic epithelial and T cells of class I proteins encoded by the major histocompatibility complex (MHC-I). Such thymic dysfunction might be responsible for a decrease of beta-cell central self-tolerance and anti-CVB4 cytotoxic CD8 T-cell activity. CVB4-induced thymic dysfunction would contribute in close association with the peripheral "bystander" effect to the destruction of insulin-secreting islet beta cells and to the development of type 1 diabetes.
authors: Université de Liège, Service d'Endocrinologie, CHU de Liège.
authors: F
authors: F
authors: Brilot
authors: V
authors: V
authors: Geenen
mesh_terms: D001324:Autoantigens; D003922:Diabetes Mellitus, Type 1 / Q000503:physiopathology* / Q000821:virology*; D029822:Enterovirus B, Human / Q000472:pathogenicity*; D004769:Enterovirus Infections / Q000150:complications*; D006801:Humans; D018716:Molecular Mimicry; D013601:T-Lymphocytes; D013950:Thymus Gland / Q000473:pathology / Q000821:virology*
chemical_list: D001324:Autoantigens