Glutathione depletion inhibits dendritic cell maturation and delayed-type hypersensitivity: Implications for systemic disease and immunosenescence

Background Dendritic cells (DCs) play a key role as antigen-presenting cells in the immune system. There is growing evidence that the redox equilibrium of these cells influences their ability to induce T-cell activation and to regulate the polarity of the immune response. This could affect the outcome of the immune response during systemic diseases and aging. Objective Our aim was to elucidate the mechanism by which the redox equilibrium of antigen-presenting DCs affects the delayed-type hypersensitivity (DTH) response during experimental modification of glutathione levels, as well as during aging. Methods We looked at the effect of glutathione depletion by diethyl maleate in DCs as well as during systemic administration on the DTH response to the contact-sensitizing antigens, oxazolone, and 2,4-dinitro-1-fluorobenzene. We also determined whether glutathione repletion with N-acetyl cysteine could influence the decline of the DTH response in aged mice. Results Glutathione depletion in bone marrow–derived DCs interfered in their ability to mount a DTH response on adoptive transfer into recipient mice. Glutathione depletion interfered in IL-12 production and costimulatory receptor expression in DCs, leading to decreased IFN-γ production in the skin of recipient mice. Systemic diethyl maleate treatment exerted similar effects on the DTH response and IFN-γ production, whereas N-acetyl cysteine administration reversed the decline of the DTH response in aged animals. Conclusion Glutathione depletion downregulates T H 1 immunity through a perturbation of DC maturation and IL-12 production. Clinical implications These data show that the induction of oxidative stress in the immune system, under disease conditions and aging, interferes in T H 1 immunity.