99th Dahlem conference on infection, inflammation and chronic inflammatory disorders: viruses, autoimmunity and immunoregulation.
Based on studies in animal models, viral infections, in particular by enteroviruses, can accelerate or halt type 1 diabetes (T1D) development. Among factors that determine the outcome are the degree of viral replication in the target organ (viral titres), the tropism of the virus for beta cells, and the precise time-point of infection in relation to the diabetogenic process. Mechanisms underlying these phenomena have been assessed in mouse studies and should now be verified for human T1D. For enhancement of diabetes development, up-regulation of interferon pathways, expression of class-I major histocompatibility complexes and Toll-like receptor-dependent immunity appear important. In contrast, prevention of T1D involves pathways that the immune system usually invokes to shut down anti-viral responses to limit immunopathology, and which can 'clean out' autoreactive memory effector T cells as a bystander phenomenon: up-regulation of inhibitory molecules and invigoration of regulatory T cell (T(reg)) function. Importantly, these immunoregulatory processes also appear to foster and sustain persistent viral infections. Induction of immunoregulatory mechanisms, and in particular the phenotype and function of T(regs), is of interest therapeutically and will be discussed.
Filippi
C M
CM
La Jolla Institute for Allergy and Immunology, La Jolla, CA, USA. christophe@liai.org
von Herrath
M G
MG
D000818:Animals; D015551:Autoimmunity; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology* / Q000821:virology*; D004770:Enterovirus / Q000276:immunology; D006801:Humans; D007372:Interferons / Q000276:immunology; D008285:Major Histocompatibility Complex / Q000276:immunology; D051379:Mice; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000382:microbiology; D051193:Toll-Like Receptors / Q000276:immunology; D014777:Virus Diseases / Q000276:immunology*; D014780:Viruses / Q000276:immunology*
D051193:Toll-Like Receptors; D007372:Interferons