Dose dependence of oral tolerance to nickel.

The dose dependence of oral nickel tolerance was analyzed by comparing three different subsets of C57BL/6 mice: Ni(very low) mice were reared in a nickel-reduced environment, Ni(low) and Ni(high) mice were reared in a stainless steel-containing environment and the latter received oral NiCl(2) (10 mM). In spleen and feces, Ni(very low) mice exhibit significantly lower nickel concentrations than Ni(low) and Ni(high) mice. In contrast to Ni(very low) mice that can be sensitized with a single intradermal administration of NiCl(2) alone, Ni(low) mice can only be sensitized in the presence of an adjuvant and Ni(high) mice cannot be sensitized at all.

Chemokine responses distinguish chemical-induced allergic from irritant skin inflammation: memory T cells make the difference.

Background: As clinical and histological features of allergic and irritant contact dermatitis share common characteristics, the differentiation between them in the preclinical and clinical evaluations of chemicals remains difficult.

Objective: To identify the differences in the underlying immunological mechanisms of chemical-induced allergic or irritant skin responses.

Methods: We systematically studied the involvement of chemokines in both diseases by quantitative real-time polymerase chain reaction in mice and humans.

Oral nickel tolerance: Fas ligand-expressing invariant NK T cells promote tolerance induction by eliciting apoptotic death of antigen-carrying, effete B cells.

Whereas oral nickel administration to C57BL/6 mice (Ni(high) mice) renders the animals tolerant to immunization with NiCl2 combined with H2O2 as adjuvant, as determined by ear-swelling assay, it fails to tolerize Jalpha18-/- mice, which lack invariant NKT (iNKT) cells. Our previous work also showed that Ni(high) splenic B cells can adoptively transfer the nickel tolerance to untreated (Ni(low)) recipients, but not to Jalpha18-/- recipients. In this study, we report that oral nickel administration increased the nickel content of splenic Ni(high) B cells and up-regulated their Fas expression while down-regulating expression of bcl-2 and Bcl-xL, thus giving rise to an Ag-carrying, apoptosis-prone B cell phenotype.

[Tolerance induction towards nickel. From animal model to humans].

Nickel is the most common contact allergen in humans. Until recently, many questions concerning tolerance mechanisms to nickel were unresolved. Besides human ex vivo, intervention and observation studies, the establishment of a reproducible mouse model has contributed to the analysis of these mechanisms.