Dose dependence of oral tolerance to nickel

作者：Wu Xianzhu; Roelofs Haarhuis Karin; Zhang Jianhong; Nowak Michael; Layland Laura; Jermann Erich; Gleichmann Ernst^*

来源：International Immunology, 2007, 19(8): 965-975.

DOI：10.1093/intimm/dxm066

• allergy
• nickel
• regulatory T cells
• tolerance/suppression

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 NiCl2 (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 NiCl2 alone, Ni-low mice can only be sensitized in the presence of an adjuvant and Ni-high mice cannot be sensitized at all. This dose-dependent resistance to nickel sensitization (i.e. Ni-high > Ni-low > Ni-very low) correlates with differences in the number and type of nickel-specific T regulatory (Treg) cells. Adoptive transfer studies into Ni-very low recipients showed that Ni-very low mice completely lack specific Treg cells whereas Ni-low and Ni-high mice harbor them, albeit their numbers and/or suppressive strength are much higher in Ni high than Ni low mice. The principal Treg subset in Ni low mice consists of CD4(+) CD25(+) cells, among which CD4(+) CD25(+) alpha(E)beta(+)(7) cells are the most effective. In Ni-high mice, CD4(+) CD25(+) Treg cells co-exist with an ensemble of CD8(+) Treg and CD4(+)CD25-suppressor-inducer cells.

• 出版日期2007-8
• 单位河北医科大学