Viral Trigger for Type 1 Diabetes: Pros and Cons
Christophe M. Filippi; Matthias G. von Herrath

Introduction
The most popular hypothesis circulating within and beyond the scientific community is that viral infections enhance or elicit autoimmune disorders such as type 1 diabetes. Indeed, viruses can injure â-cells and have been isolated in pancreatic tissues from diabetic patients. However, accumulating evidence suggests that the opposite scenario, which is prevention or amelioration of type 1 diabetes, might be at least as common an outcome of viral infection. Here, we discuss epidemiological and experimental evidence for the main mechanisms accounting for the role of viruses in type 1 diabetes to better understand the complex relationship between viral infections and autoimmune diabetes.


The Influence of the Environment
Type 1 diabetes is a genetic autoimmune disorder caused by autoreactive CD4+ and CD8+ T-cells that recognize pancreatic antigens such as insulin or GAD and subsequently destroy insulin-producing â-cells. The subject of very active research is the question of how endogenous â-cell antigens become immunogenic. Infiltration of the islets of Langerhans, where â-cells reside, by activated autoreactive T-cells is considered to be the major driving force in type 1 diabetes progression. The islet infiltrate in humans consists primarily of CD8+ T-cells and B-cells, followed by macrophages and dendritic cells of different subtypes. Interestingly, significantly fewer T-cells are found in human islets compared with islets from nonobese diabetic (NOD) mice. The reduced numbers of T-cells, and in this way a limited autoreactive component in human islets, leads one to consider whether other contributing factors may be involved in disease development. Otherwise, sufficient insulitic infiltrate to destroy islet â-cells might not be easily maintained in humans. Further supporting a role for nongenetic factors in the control of type 1 diabetes is the observation that disease concordance among monozygotic twins is below 50%.

Migrant studies also suggest the involvement of an environmental factor in type 1 diabetes, since disease incidence in migrating populations appears to conform to the incidence of the region to which there is migration. There is an ever-increasing body of literature suggesting that the significant environmental component to type 1 diabetes development and progression is a viral infection. However, this has not been clearly demonstrated. In fact, viral infections appear to have both detrimental and protective effects on type 1 diabetes development, which might be contingent upon the nature of the virus, but also the immune status of the host and thus the timing of infection.

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