Viral infection enables CD4+CD25+ regulatory T cells to protect from autoimmune diabetes (128.9)

Abstract

Abstract While viral infections may be capable of triggering autoimmune diabetes (T1D) in genetically susceptible individuals, accumulating evidence indicates that viruses can also prevent T1D. However, the underlying mechnisms are only partially understood. Here, we show that activation of CD4+CD25+ Tregs by acute lymphocytic choriomeningitis virus (LCMV) infection provides these cells with the capacity to prevent both spontaneous and virally induced T1D in the mouse. We found that CD4+CD25+ Tregs activated by LCMV in vivo or in vitro produce the regulatory cytokine TGF-b and are capable of protecting NOD and RIP-LCMV mice from spontaneous and LCMV-induced diabetes, respectively. Our results suggest that LCMV-modulated CD4+CD25+ Tregs act in a bystander fashion independent of beta-cell antigens and suppress TNF-a production by autoreactive CD8+ T cells, leading to prevention of T1D. These findings provide a novel mechanistic explanation for the previously reported ability of viral infections to prevent autoimmune diabetes. Furthermore, our results support a model explaining the differential ability of viral infections to modulate diabetes. Activation of Tregs during viral infections may be a general feature accounting for the ability of viruses to prevent T1D as well as other autoimmune disorders.