title: TSST-1 induces Th1 or Th2 differentiation in naïve CD4+ T cells in a dose- and APC-dependent manner.
abstract: Superantigens are potent activators of the immune system, causing a variety of diseases, ranging from food poisoning to septic shock. Here, we examined the effects of different toxic shock syndrome toxin 1 (TSST-1) concentrations on the activation, proliferation and synthesis of interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) in purified naïve human CD4+ T cells in a serum-free in vitro system. TSST-1 given in low doses (1-10 pg/ml) generates a pronounced T helper 2 (Th2)-like cytokine profile, characterized by elevated IL-4-expressing T-cell populations and reduced IFN-gamma-producing populations, whereas higher doses (100 pg/ml) induce a Th1-like profile, with increased expression of IFN-gamma and reduced expression of IL-4. These patterns were even more pronounced by adding exogenous cytokines like IL-12 and IL-4 and by the type of antigen-presenting cells (APCs). Thus, B cells induced Th2 shifts, whereas monocytes favoured Th1 induction. Moreover, IL-12 in conditions with B cells counteracted their Th2 bias. Interestingly, in purified naïve T-cell cultures, containing a small population of HLA-DR+ T cells, Th1/Th2 differentiation can be induced by TSST-1 too. There, Th-cell polarization is strongly dependent on TSST-1 concentration, indicating that this is a key parameter in regulating the differentiation of T cells. In conclusion, our data show that Th1/Th2 differentiation of TSST-1-stimulated naïve T cells is controlled by the type of APCs, and in APC-depleted cultures, it depends on the presence of HLA-DR+ cells and TSST-1 concentration.
authors.affiliation: Division of Experimental Immunopharmacology, Medical Clinic Research Center Borstel, Borstel, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Brandt
authors.forename: J
authors.initials: J
authors.lastname: van der Bosch
authors.forename: R
authors.initials: R
authors.lastname: Fliegert
authors.forename: S
authors.initials: S
authors.lastname: Gehring
mesh_terms: D017951:Antigen Presentation; D000938:Antigen-Presenting Cells / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology; D001427:Bacterial Toxins; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002454:Cell Differentiation; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D004306:Dose-Response Relationship, Immunologic; D004768:Enterotoxins / Q000276:immunology*; D006684:HLA-DR Antigens / Q000096:biosynthesis; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D008213:Lymphocyte Activation; D018089:Superantigens / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*
chemical_list: D001427:Bacterial Toxins; D016207:Cytokines; D004768:Enterotoxins; D006684:HLA-DR Antigens; D018089:Superantigens; C030107:enterotoxin F, Staphylococcal; D015847:Interleukin-4; D007371:Interferon-gamma