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In this issue

There is a growing need for geneticallymodified dendritic cells (DCs) to treat autoimmune diseases and allergies. Such gene-modified DCs should, however, be in a low activation state when considering therapeutic strategies intended to induce tolerance. Here, Besche et al. demonstrate that gene transduction by recombinant lentiviruses leads to partial activation of DCs via the associated physical stress. Mock-transduced DCs displayed an altered gene expression signature and an increased T cell stimulatory capacity. However, IL-10 overexpression counteracted the stress-induced DC activation and led to a tolerogenic state. Indeed, IL-10-overexpressing DCs efficiently inhibited the contact hypersensitivity response in previously haptensensitized mice. Therefore, lentivirallytransduced DCs expressing immunomodulatory molecules, which prevent DC activation in an autocrine manner, may constitute promising tools for the induction of tolerance.