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