Activation of nickel-specific CD4+ T lymphocytes in the absence of professional antigen-presenting cells

Francesca Nasorri, Silvia Sebastiani, Valentina Mariani, Ornella De Pità, Pietro Puddu, Giampiero Girolomoni, Andrea Cavani

Research output: Contribution to journalArticlepeer-review


Allergic contact dermatitis ensues from exaggerated T cell responses to haptens. Dendritic cells are required for the initiation of hapten sensitization, but they may not be necessary for disease expression. Here we investigated the antigen-presenting cell requirement of nickel-specific CD4+ lymphocytes isolated from the blood of six allergic individuals. A significant proportion (42 out of 121; 35%) of the T cell clones proliferated in vitro to nickel also in the absence of professional antigen-presenting cells, suggesting a direct T-T hapten presentation. Antigen-presenting-cell-independent T cells showed a predominant T helper 1 phenotype. Nickel recognition by these T cells was major histocompatibility complex class II restricted, not influenced by CD28 triggering, independent from their state of activation, and did not require processing. The capacity of this T cell subset to be directly stimulated by nickel was not due to unique antigen-presenting properties, as both antigen-presenting-cell-dependent and antigen-presenting-cell-independent clones displayed comparable levels of HLA-DR, CD80, and CD86, and were equally capable of presenting nickel to antigen-presenting-cell-independent clones. In contrast, neither T cell types activated antigen-presenting-cell-dependent T lymphocytes. T-T presentation induced T cell receptor downregulation, CD25, CD80, CD86, and HLA-DR upregulation, and interferon-γ release, although to a lesser extent compared to those induced by dendritic cell-T presentation. Following T-T presentation, the clones did not undergo unresponsiveness and maintained the capacity to respond to dendritic cells pulsed with antigen. In aggregate, our data suggest that antigen-presenting-cell-independent T cell activation can effectively amplify hapten-specific immune responses.

Original languageEnglish
Pages (from-to)172-179
Number of pages8
JournalJournal of Investigative Dermatology
Issue number1
Publication statusPublished - 2002


  • Allergy
  • Antigen presentation
  • Nickel
  • Skin
  • T lymphocytes

ASJC Scopus subject areas

  • Dermatology


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