Viral Trigger for Type 1 Diabetes
Pros and Cons
- From the La Jolla Institute for Allergy and Immunology, La Jolla, California
- Corresponding author: Matthias von Herrath,
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 β-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.
INSIGHT FROM EPIDEMIOLOGY AND CLINICAL INVESTIGATIONS
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 β-cells. The subject of very active research is the question of how endogenous β-cell antigens become immunogenic. Infiltration of the islets of Langerhans, where β-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 (1). 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 β-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% (2). Migrant studies also suggest the involvement of an environmental factor in type 1 diabetes, …