In vivo reprogramming of UV radiation-induced regulatory T-cell migration to inhibit the elicitation of contact hypersensitivity

Background: Regulatory T (Treg) cells induced by UV radiation (UVR) inhibit only the induction and not the elicitation of contact hypersensitivity (CHS) because they migrate into the lymph nodes but not the skin. The tissue-homing receptor expression and migratory behavior of Treg cells can be altered by means of in vitro coincubation with skin-derived antigen-presenting cells. On this in vitro treatment, Treg cells migrate into the skin and thus inhibit the elicitation of CHS. Objective: We attempted to determine whether Treg cells can be induced by UVR in sensitized mice and manipulated entirely in vivo in such a way that they suppress the elicitation of immune responses. Methods: Treg cells were induced by applying contact allergens onto UV-exposed skin in wild-type, langerin diphtheria toxin receptor knock-in, or depletion of Treg cell transgenic mice. Results: UVR-induced Treg cells inhibit the elicitation of CHS in sensitized mice when stimulated by means of an antigen-specific boost through the skin. This requires cutaneous antigen-presenting cells that alter the migratory behavior of Treg cells and drive them out of the lymph nodes into the skin. Conclusions: The indication is that antigen-specific Treg cells can be induced in sensitized hosts and manipulated in such a way that they suppress the elicitation of specific immune reactions. Because this is achieved entirely in vivo without invasive interventions, our findings might have important implications for strategies aiming to induce and use Treg cells in a therapeutic setting. (J Allergy Clin Immunol 2011;128:826-33.)