title: The intensity of T cell receptor engagement determines the cytokine pattern of human allergen-specific T helper cells.
abstract: Enhanced production of T helper (Th)2 cytokines by allergen-specific Th cells plays a major role in the induction and maintenance of IgE-mediated allergic disorders. The mechanism that triggers this type of response in atopic individuals is not fully understood. Allergen-specific human Th cell clones produce interleukin (IL)-4 and low or undetectable levels of interferon (IFN)-gamma after stimulation with low concentrations of antigen. However, these Th cell clones are capable of generating significant amounts of IFN-gamma after optimal activation through their T cell receptor (TcR). Allergen-specific Th cell clones isolated from allergic individuals required higher doses of antigen to reach the plateau of proliferation and to generate Th0 cytokine responses than their counterparts isolated from nonallergic subjects. On the other hand, if allergen was replaced by anti-CD3 monoclonal antibody (mAb), both allergic and nonallergic Th cell clones attained the highest level of proliferation and significant IFN-gamma production in response to equivalent concentrations of anti-CD3 mAb. These results indicate that the strength of T cell ligation, which can be modulated by the availability of the TcR ligand, controls the balance of Thl/Th2 cytokines produced by memory Th cells in vitro. In the particular case of bee venom phospholipase A2, it is shown that the expression of allergen-specific surface Ig on antigen-presenting B cells has little influence on antigen uptake and therefore in determining the levels of T cell activation and cytokine production. Alternatively, the affinity of particular major histocompatibility complex class II molecules on antigen-presenting cells for allergen-derived peptides might determine the amount of specific ligand presented to the Th cells and play a decisive role skewing the Th cell cytokine production towards Th1 or Th2 phenotypes. These findings, which are consistent with the changes in cytokine patterns observed following clinical hyposensitization, suggest that polarized human Th2 cell subsets still retain the capacity to modulate their cytokine pattern.
authors.affiliation: Swiss Institute of Allergy and Asthma Research (SIAF), Davos.
authors.forename: J M
authors.initials: JM
authors.lastname: Carballido
authors.forename: A
authors.initials: A
authors.lastname: Faith
authors.forename: N
authors.initials: N
authors.lastname: Carballido-Perrig
authors.forename: K
authors.initials: K
authors.lastname: Blaser
mesh_terms: D000485:Allergens / Q000276:immunology*; D016207:Cytokines / Q000032:analysis* / Q000096:biosynthesis*; D006801:Humans; D007156:Immunologic Memory / Q000276:immunology*; D007371:Interferon-gamma / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D011485:Protein Binding / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000276:immunology / Q000378:metabolism*; D006377:T-Lymphocytes, Helper-Inducer / Q000378:metabolism*; D018417:Th1 Cells / Q000378:metabolism; D018418:Th2 Cells / Q000378:metabolism
chemical_list: D000485:Allergens; D016207:Cytokines; D011948:Receptors, Antigen, T-Cell; D015847:Interleukin-4; D007371:Interferon-gamma