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RESEARCH PRODUCT
Critical role of IL-10 in the induction of low zone tolerance to contact allergens
Martin MetzKerstin SteinbrinkJuergen KnopWolfgang Seidel-guyenotMarcus Maurersubject
CD4-Positive T-LymphocytesAdoptive cell transferPopulationPicryl ChlorideBiologyCD8-Positive T-LymphocytesDermatitis ContactArticleImmune tolerancePicryl chloridechemistry.chemical_compoundMiceImmune systemmedicineImmune ToleranceAnimalseducationLymph nodeMice Knockouteducation.field_of_studyGeneral MedicineAllergensAdoptive TransferInterleukin-10Mice Inbred C57BLInterleukin 10medicine.anatomical_structurechemistryImmunologyCD8description
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.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2003-08-01 |