title: Activation of nickel-specific CD4+ T lymphocytes in the absence of professional antigen-presenting cells.
abstract: 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.
authors.affiliation: Laboratory of Immunology and Department of Immunodermatology, Istituto Dermopatico dell' Immacolata, IRCCS, Rome, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Nasorri
authors.forename: Silvia
authors.initials: S
authors.lastname: Sebastiani
authors.forename: Valentina
authors.initials: V
authors.lastname: Mariani
authors.forename: Ornella
authors.initials: O
authors.lastname: De Pità
authors.forename: Pietro
authors.initials: P
authors.lastname: Puddu
authors.forename: Giampiero
authors.initials: G
authors.lastname: Girolomoni
authors.forename: Andrea
authors.initials: A
authors.lastname: Cavani
mesh_terms: D000328:Adult; D000938:Antigen-Presenting Cells / Q000502:physiology; D015703:Antigens, CD / Q000378:metabolism; D018122:B7-1 Antigen / Q000378:metabolism; D051940:B7-2 Antigen; D018106:CD28 Antigens / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D015536:Down-Regulation / Q000502:physiology; D005260:Female; D006241:Haptens / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000032:analysis / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D008213:Lymphocyte Activation / Q000502:physiology*; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D009532:Nickel / Q000276:immunology*; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D018106:CD28 Antigens; C497964:CD86 protein, human; D006241:Haptens; D000949:Histocompatibility Antigens Class II; D008562:Membrane Glycoproteins; D011948:Receptors, Antigen, T-Cell; D015375:Receptors, Interleukin-2; D009532:Nickel; D007371:Interferon-gamma