title: Critical role of IL-10 in the induction of low zone tolerance to contact allergens.
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.affiliation: Department of Dermatology, University of Mainz, Mainz, Germany.
authors.forename: Marcus
authors.initials: M
authors.lastname: Maurer
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Seidel-Guyenot
authors.forename: Martin
authors.initials: M
authors.lastname: Metz
authors.forename: Juergen
authors.initials: J
authors.lastname: Knop
authors.forename: Kerstin
authors.initials: K
authors.lastname: Steinbrink
mesh_terms: D019264:Adoptive Transfer; D000485:Allergens / Q000008:administration & dosage*; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D003877:Dermatitis, Contact / Q000276:immunology / Q000517:prevention & control*; D007108:Immune Tolerance; D016753:Interleukin-10 / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010853:Picryl Chloride / Q000008:administration & dosage / Q000276:immunology
chemical_list: D000485:Allergens; D016753:Interleukin-10; D010853:Picryl Chloride