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.

SUBMITTER: Luckey U 

PROVIDER: S-EPMC3195460 | biostudies-literature | 2011 Oct

REPOSITORIES: biostudies-literature