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T cell killing by tolerogenic dendritic cells protects mice from allergy
Ulrike Luckey, … , Martin Metz, Kerstin Steinbrink
Ulrike Luckey, … , Martin Metz, Kerstin Steinbrink
Published September 1, 2011
Citation Information: J Clin Invest. 2011;121(10):3860-3871. https://doi.org/10.1172/JCI45963.
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Research Article Immunology Article has an altmetric score of 1

T cell killing by tolerogenic dendritic cells protects mice from allergy

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Abstract

It is well established that allergy development can be prevented by repeated low-dose exposure to contact allergens. Exactly which immune mechanisms are responsible for this so-called low zone tolerance (LZT) is not clear, although CD8+ suppressor T cells are known to have a role. Here, we show that TNF released by tolerogenic CD11+CD8+ DCs located in skin-draining lymph nodes is required and sufficient for development of tolerance to contact allergens in mice. DC-derived TNF protected mice from contact allergy by inducing apoptosis in allergen-specific effector CD8+ T cells via TNF receptor 2 but did not contribute to the generation and function of the regulatory T cells associated with LZT. The TNF-mediated killing mechanism was induced in an allergen-specific manner. Activation of tolerogenic DCs by LZT CD8+ suppressor T cells and enhanced TNF receptor 2 expression on contact allergen–specific CD8+ effector T cells were required for LZT. Our findings may explain how tolerance protects from allergic diseases, which could allow for the development of new strategies for allergy prevention.

Authors

Ulrike Luckey, Marcus Maurer, Talkea Schmidt, Nadine Lorenz, Beate Seebach, Martin Metz, Kerstin Steinbrink

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Figure 1

TNF and p75 are required for LZT.

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TNF and p75 are required for LZT.
(A) Release of TNF 24, 48, and 72 hour...
(A) Release of TNF 24, 48, and 72 hours after hapten-specific restimulation of lymph node cells obtained from tolerized (TNCB 4.5 μg), sensitized, and challenged mice versus mock-tolerized (solvent), sensitized, and challenged mice (n = 6 per group per experiment, data shown are pooled from 5 experiments). (B–E) Efficacy of LZT as quantified by assessing CHS-induced ear swelling and CD8+ T cell cytokine pattern and proliferation after restimulation. Data represent CHS-induced relative (B) and absolute (C) changes in ear thickness, (D) IFN-γ and IL-2 production of CD8+ T cells (detected by ELISA), and (E) T cell proliferation (in cpm, incorporation of [3H]thymidine) after hapten-specific restimulation in vitro. B–E show 1 of 3 independent experiments (5–6 mice per group), which all yielded similar results. Data are shown as mean ± SD. *P < 0.05; **P < 0.01; ***P < 0.001.

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ISSN: 0021-9738 (print), 1558-8238 (online)

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