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

J Invest Dermatol. 2002 Jan;118(1):172-9. doi: 10.1046/j.0022-202x.2001.01574.x.


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-gamma 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antigen-Presenting Cells / physiology
  • Antigens, CD / metabolism
  • B7-1 Antigen / metabolism
  • B7-2 Antigen
  • CD28 Antigens / immunology
  • CD4-Positive T-Lymphocytes / immunology*
  • Down-Regulation / physiology
  • Female
  • Haptens / immunology
  • Histocompatibility Antigens Class II / analysis
  • Histocompatibility Antigens Class II / immunology
  • Humans
  • Interferon-gamma / metabolism
  • Lymphocyte Activation / physiology*
  • Male
  • Membrane Glycoproteins / metabolism
  • Nickel / immunology*
  • Receptors, Antigen, T-Cell / metabolism
  • Receptors, Interleukin-2 / metabolism
  • Up-Regulation


  • Antigens, CD
  • B7-1 Antigen
  • B7-2 Antigen
  • CD28 Antigens
  • CD86 protein, human
  • Haptens
  • Histocompatibility Antigens Class II
  • Membrane Glycoproteins
  • Receptors, Antigen, T-Cell
  • Receptors, Interleukin-2
  • Nickel
  • Interferon-gamma