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Critical role of IL-10 in the induction of low zone tolerance to contact allergens
Marcus Maurer, … , Juergen Knop, Kerstin Steinbrink
Marcus Maurer, … , Juergen Knop, Kerstin Steinbrink
Published August 1, 2003
Citation Information: J Clin Invest. 2003;112(3):432-439. https://doi.org/10.1172/JCI18106.
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Article Immunology

Critical role of IL-10 in the induction of low zone tolerance to contact allergens

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Abstract

The development and mechanisms of tolerance to allergens are poorly understood. Using the murine low zone tolerance (LZT) model, where contact hypersensitivity (CHS) is prevented by repeated topical low-dose applications of contact allergens, we show that LZT induction is IL-10 dependent. IL-10 is required for the generation of LZT effector cells, that is, CD8+ regulatory T cells. Only T cells from tolerized IL-10+/+ mice or IL-10–/– mice reconstituted with IL-10 during LZT induction adoptively transferred LZT to naive mice and prevented CHS, whereas T cells from IL-10–/– mice failed to do so. The IL-10 required for normal LZT development is derived from lymph node CD4+ T cells, the only skin or lymph node cell population found to produce relevant amounts of IL-10 after tolerization. CD4+ T cells derived from IL-10+/+ mice, but not from IL-10–/– mice, allowed the induction of LZT in adoptively transferred T cell–deficient mice. Interestingly, IL-10 injections during tolerization greatly enhanced LZT responses in normal mice. Thus, the generation of CD8+ LZT effector T cells by CD4+ regulatory T cells via IL-10 may be a promising target of strategies aimed at preventing contact allergies and other harmful immune responses.

Authors

Marcus Maurer, Wolfgang Seidel-Guyenot, Martin Metz, Juergen Knop, Kerstin Steinbrink

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Figure 1

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IL-10 is required for the induction of LZT, whereas CHS prevention in to...
IL-10 is required for the induction of LZT, whereas CHS prevention in tolerized mice is IL-10 independent. Expression of LZT quantified by assessing allergic inflammatory responses (ear swelling) after TNCB challenge in IL-10+/+ mice and IL-10–/– mice that were treated repeatedly with low doses of contact allergen (TNCB) to induce LZT and then sensitized to TNCB. Some IL-10–/– mice were reconstituted with IL-10 during tolerization (the induction phase of LZT) or during sensitization (the effector phase of LZT). Data represent relative (a) and absolute (b) changes in ear thickness (means ± SEM) pooled from six or more mice per treatment group from one of three independent experiments with similar results. #P < 0.001.

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

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