Human CD25+ Regulatory T Cells Maintain Immune Tolerance to Nickel in Healthy, Nonallergic Individuals

Andrea Cavani, Francesca Nasorri, Chiara Ottaviani, Silvia Sebastiani, Ornella De Pità, Giampiero Girolomoni

Research output: Contribution to journalArticlepeer-review


We investigated the capacity of CD25+ T regulatory cells (Treg) to modulate T cell responses to nickel, a common cause of allergic contact dermatitis. CD4+ T cells isolated from the peripheral blood of six healthy, nonallergic individuals showed a limited capacity to proliferate in response to nickel in vitro, but responsiveness was strongly augmented (mean increment ± SD, 240 ± 60%) when cells were depleted of CD25 + Treg. Although CD25+ Treg were anergic to nickel, a small percentage up-regulated membrane CTLA-4 upon nickel exposure. CD25 + Treg strongly and dose-dependently inhibited nickel-specific activation of CD25- T lymphocytes in coculture experiments in a cytokine-independent, but cell-to-cell contact-dependent, manner. Approximately 30% of circulating CD25+ Treg expressed the cutaneous lymphocyte-associated Ag (CLA), and CLA+CD25+ Treg were more efficient than CLA-CD25+ cells in suppressing nickel responsiveness of CD25- T cells. The site of a negative patch test in response to nickel showed an infiltrate of CD4+CLA+ cells and CD25+ cells, which accounted for ∼20% of the total T cells isolated from the tissue. Skin-derived T cells suppressed nickel-specific responses of peripheral blood CD25- T cells. In addition, 60 ± 14% of peripheral blood CD25+ Treg expressed the chemokine receptor CCR7 and strongly inhibited naive T cell activation in response to nickel. Finally, CD25+ T cells isolated from peripheral blood of nickel-allergic patients showed a limited or absent capacity to suppress metal-specific CD4+ and CD8+ T cell responses. The results indicates that in healthy individuals CD25+ Treg can control the activation of both naive and effector nickel-specific T cells.

Original languageEnglish
Pages (from-to)5760-5768
Number of pages9
JournalJournal of Immunology
Issue number11
Publication statusPublished - Dec 1 2003

ASJC Scopus subject areas

  • Immunology


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