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

T cell killing by tolerogenic dendritic cells protects mice from allergy

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 8

CD8+CD11c+ DC–derived TNF is essential for LZT.

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CD8+CD11c+ DC–derived TNF is essential for LZT. LZT responses measur...
LZT responses measured by assessing inhibition of CHS-associated ear swelling (A, C, E, and G) and T cell proliferation (B, D, F, and H) in tolerized and sensitized (white bars and white symbols) or mock-tolerized and sensitized (solvent-treated; black bars and symbols) WT mice and Tnf–/– mice, in Tnf–/– mice that were first adoptively transferred with highly purified (>99.9%) CD8+CD11c– T cells or CD8+CD11c+ DCs isolated from naive WT mice and then sensitized (A and B), in Tnf–/– mice that were first adoptively transferred with highly purified CD8+CD11c+ DCs isolated from naive Tnf–/– or WT mice and then sensitized (C and D), in Tnf–/– mice that were first adoptively transferred with highly purified CD8-negative CD11c+ DCs isolated from naive WT animals and then sensitized (E and F), or in Tnf–/– mice that were first adoptively transferred with highly purified CD8+CD11c+ DCs isolated from naive memTnf–/– mice and then sensitized (G and H). 1 of 2 independent experiments with similar results is shown (5–6 mice per group and per experiment). Data are shown as mean ± SD. *P < 0.05; **P < 0.01; ***P < 0.001.