Conditioning of naïve CD4(+) T cells for enhanced peripheral Foxp3 induction by non-specific bystander inflammation

Inflammation induced during infection can both promote and suppress immunity. This contradiction suggests that inflammatory cytokines impact the immune system in a context-dependent manner. Here we show that non-specific bystander inflammation conditioned naïve CD4(+) T cells for enhanced peripheral Foxp3 induction and reduced effector differentiation. This resulted in inhibition of immune responses in vivo via Foxp3-dependent effect on antigen-specific naïve CD4(+) T cell precursors. Such conditioning may have evolved to allow immunity to infection while limiting subsequent autoimmunity caused by release of self-antigens in the wake of infection. Furthermore, this phenomenon suggests a mechanistic explanation for the concept that early tuning of the immune system by infection impacts the long-term quality of immune regulation.