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Virus Infections and Type 1 Diabetes


The relationship between infections and autoimmunity is complex. Current evidence indicates that microbes can initiate, enhance or, conversely, abrogate autoimmunity. Microbial infections can act as environmental triggers inducing or promoting autoimmunity resulting in clinical manifestations of autoimmune disease in genetically predisposed individuals. However, increasing evidence suggests the opposite outcome, which is the prevention or amelioration of autoimmune processes following microbial encounters. These latter observations support conceptually the ‘hygiene hypothesis’ suggesting that cleaner living conditions will lead to enhanced incidence of autoimmune disorders, asthma and allergies. Since proof of concept in humans is difficult to obtain, we will discuss relevant animal model data in context with likely or proven human associations. Knowledge of mechanisms that underlie either positive or negative effects of infections on autoimmunity will facilitate exploration of molecular details for prospective clinical studies in the future.

Abrogation of type 1 diabetes by virus infection
Infection at another location might keep autoaggressive cells from reaching the site
of autoimmune destruction. It is this last possibility that may be responsible for the abrogation of T1D in NOD mice after LCMV-infection that was initially observed more than a decade ago. We recently demonstrated that infection of NOD and LCMV-immune RIP-LCMV mice with LCMV abrogated T1D.  We proposed that this occurred because the ‘abrogative’ virus grew predominantly in lymphoid organs and other sites rather than the pancreas or islets themselves (Christen et al (2004) J. Clin. Invest.113: 74-84). Infection with LCMV in these scenarios caused inflammation of the PDLN characterized by extensive expression of the chemokine CXCL10. This resulted in accumulation of autoaggressive T cells in PDLN rather than the islets and lack of development of clinical disease (Christen et al (2004) J. Clin. Invest.113: 74-84). Interestingly, the protection from diabetes was permanent, possibly because many autoaggressive lymphocytes had been permanently deleted as indicated by an enhanced frequency of islet-specific CD8 T-cells undergoing apoptosis in the PDLN after LCMV infection (Christen et al (2004) J. Clin. Invest.113: 74-84). In a sense, sites of strong inflammation might therefore act as a ‘filter’ for autoaggressive T cells eliminating them from the circulation and preventing them from reaching the pancreatic islets. Similar mechanisms might be at work in other scenarios, where infections protect from autoimmunity.