Synthetic fragments of the NS1 protein of the tick-borne encephalitis virus exhibiting a protective effect

Potentially immunoactive regions of the NS1 nonstructural protein of the tick-borne encephalitis virus that can stimulate the antibody formation in vivo and protect animals from this disease were chosen on the basis of theoretical calculations. Eleven 16-to 27-aa peptides containing the chosen regions were synthesized. The ability of the free peptides (without any high-molecular-mass carrier) to stimulate the production of antipeptide antibodies in mice of three lines and ensure the formation of protective immunity was studied. Most of these peptides were shown to exhibit the immunogenic activity in a free state. Five fragments that can protect mice from the infection by a lethal dose of tick-borne encephalitis virus were found.     

A novel subset of helper T cells promotes immune responses by secreting GM-CSF

Helper T cells are crucial for maintaining proper immune responses. Yet, they have an undefined relationship with one of the most potent immune stimulatory cytokines, granulocyte macrophage-colony-stimulating factor (GM-CSF). By depleting major cytokines during the differentiation of CD4⁺ T cells in vitro, we derived cells that were found to produce large amounts of GM-CSF, but little of the cytokines produced by other helper T subsets. By their secretion of GM-CSF, this novel subset of helper T cells (which we have termed ThGM cells) promoted the production of cytokines by other T-cell subtypes, including type 1 helper T cell (Th1), type 2 helper T cell (Th2), type 1 cytotoxic T cell (Tc1), type 2 cytotoxic T cell (Tc2), and naive T cells, as evidenced by the fact that antibody neutralization of GM-CSF abolished this effect. ThGM cells were found to be highly prone to activation-induced cell death (AICD). Inhibitors of TRAIL or granzymes could not block AICD in ThGM cells, whereas inhibition of FasL/Fas interaction partially rescued ThGM cells from AICD. Thus, ThGM cells are a novel subpopulation of T helper cells that produce abundant GM-CSF, exhibit exquisite susceptibility to apoptosis, and therefore play a pivotal role in the regulation of the early stages of immune responses.     

Hypoxia enhances stimulating effect of amyloid beta peptide (25–35) for interleukin 17 and T helper lymphocyte subtype 17 upregulation in cultured peripheral blood mononuclear cells

Th17 has been demonstrated to have a key role in several autoimmune diseases. The present study was carried out to investigate changes in IL-17 and Th17 in cultured PBMC in response to Abeta peptide (25–35) and hypoxic stimulation in vitro . PBMC were collected from adult healthy donors and cultured in normal and anaerobic conditions (hypoxia 1, 3, 6, 12, 24 hr). Each group of cells was stimulated with Abeta peptide (25–35; 3, 10 nmol/ml). ELISA was used to examine IL-17A concentrations in the supernatants, and flow cytometry for the numbers of IL-17A secreting CD4 positive Th17 lymphocytes. Statistically significant increases in IL-17A and Th17 concentrations were found in groups with 10 nmol/ml Abeta (25–35) and more than three hr anaerobic culture. IL-17A and Th17 concentrations in anaerobic groups increased gradually with time and peaked at six hr. Compared with other groups, the highest concentrations were found in those treated with 10 nmol/ml Abeta and cultured for six hr ( P < 0.001). This study provides the first report that IL-17A and Th17 lymphocytes are possibly involved in the immune pathogenesis caused by Abeta peptide (25–35). Hypoxia may enhance this response independently of time.     

Mechanisms that promote the evolution of cross-reactive antibodies upon vaccination with designed influenza immunogens

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