Dose dependence of oral tolerance to nickel

Area of Science:

• Immunology
• Toxicology
• Environmental Health

Background:

• Nickel is a common environmental and industrial metal.
• Understanding nickel's impact on immune tolerance is crucial for public health.
• Previous research suggests varying immune responses to nickel exposure.

Purpose of the Study:

• To investigate the dose-dependent effects of oral nickel exposure on immune tolerance in C57BL/6 mice.
• To identify the role of T regulatory cells (Treg) in mediating nickel tolerance.
• To characterize the specific subsets of Treg cells involved in nickel tolerance.

Main Methods:

• Comparison of three mouse groups with varying oral nickel exposure: very low, low, and high (NiCl2, 10 mM).
• Analysis of nickel concentrations in spleen and feces.
• Assessment of nickel sensitization following intradermal NiCl2 administration with or without adjuvant.
• Adoptive transfer studies using T regulatory cells from different exposure groups.

Main Results:

• Higher oral nickel exposure resulted in increased nickel concentrations in spleen and feces.
• Nickel tolerance increased with dose: Ni(very low) mice were easily sensitized, Ni(low) required adjuvant, and Ni(high) were resistant to sensitization.
• Dose-dependent resistance correlated with the number and type of nickel-specific T regulatory cells (Treg).
• Ni(low) mice primarily utilized CD4(+)CD25(+)alpha(E)beta(7)(+) Treg cells, while Ni(high) mice also had CD8(+) Treg and CD4(+)CD25(-) suppressor-inducer cells.

Conclusions:

• Oral nickel exposure induces dose-dependent immune tolerance, mediated by nickel-specific T regulatory cells.
• The composition and suppressive capacity of Treg cells vary with nickel exposure levels.
• These findings provide insights into the mechanisms of metal-induced immune tolerance and potential implications for allergy and autoimmunity.