Regulation of nickel-induced T-cell responsiveness by CD4⁺CD25⁺cells in contact allergic patients and healthy individuals

In this study, we investigated the capacity of CD4⁺CD25⁺ regulatory T cells to suppress nickel-specific effector T cells, both in nickel-allergic patients and healthy controls. CD4⁺ cells isolated from allergic patients showed an increased proliferative response to nickel, whereas CD4⁺ cells from negative controls did not respond to allergen. When CD4⁺CD25⁺ cells were depleted, nickel-specific responsiveness was strongly increased both in allergic and in non-allergic individuals, with the most pronounced effect in allergic patients. These regulatory T cells were anergic to nickel but inhibited nickel-specific CD4⁺CD25^– effector T cells in coculture experiments. CD4⁺CD25⁺ cells from nickel-allergic patients showed only a limited capacity to suppress effector T-cell responsiveness, because an increased nickel reactivity could still be detected in these cocultures. None of the isolated CD4⁺CD25⁺ cells, either isolated from healthy controls or allergic patients, produced IL-10 in response to nickel. Overall, these results support the view that CD4⁺CD25⁺ cells can control the activation of nickel-specific effector T cells in non-allergic individuals, whereas this regulatory capacity is impaired in allergic patients. To investigate the presence of allergen-specific regulatory T cells in truly naïve, non-sensitized individuals, T-cell reactivity should also be studied with non-environmental contact allergens, such as para-phenylenediamine.