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.

Oral tolerance to nickel requires CD4+ invariant NKT cells for the infectious spread of tolerance and the induction of specific regulatory T cells.

Previously, oral administration of nickel to C57BL/6 wild-type (WT) mice was shown to render both their splenic T cells and APCs (i.e., T cell-depleted spleen cells) capable of transferring nickel tolerance to naive syngeneic recipients.

Drug-induced autoantibody formation in mice: triggering by primed CD4+CD25- T cells, prevention by primed CD4+CD25+ T cells.

Although the ability of CD4+CD25+ T suppressor (Ts) cells to prevent experimental autoimmune diseases has been described, nothing is known concerning their role and mechanism of action in xenobiotic-induced autoimmunity. Procainamide, mercuric chloride, and gold(I) are three xenobiotics that can induce autoimmune reactions in humans and rodents. After the induction of IgG1 antinuclear autoantibodies (ANA) in mice treated with either of the above xenobiotics, adoptive transfer of their CD4+CD25+ T cells completely prevented ANA formation in recipients treated with the same xenobiotic; transfer of CD8+ T cells was ineffective.

Infectious nickel tolerance: a reciprocal interplay of tolerogenic APCs and T suppressor cells that is driven by immunization.

Previously, we reported that tolerance to nickel, induced by oral administration of Ni(2+) ions, can be adoptively transferred to naive mice with only 10(2) splenic T cells. Here we show that 10(2) T cell-depleted spleen cells (i.e.

Cross-sensitization to haptens: formation of common haptenic metabolites, T cell recognition of cryptic peptides, and true T cell cross-reactivity.

To analyze T cell cross-reactivity to para-compounds, we established CD4(+) T cell hybridomas from mice immunized with adducts of self-globin and one of three different para-compounds: p-aminophenol, p-phenylenediamine, or Bandrowski's base. Some of the hybridomas obtained reacted not only to the immunizing antigen, but also to metabolically related para-compounds, bound to the same protein, thus suggesting formation of common metabolites. Other hybridomas cross-reacted to globin adducts of metabolically unrelated para-compounds, which denotes them as truly cross-reactive cells whose TCR failed to distinguish among the different haptens.