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• W2035006354 abstract "An imbalance in the Th1- and Th2-type cytokine responses may allow certain microbes to modify the host response to favor their own persistence. We now show that infection/pulsing of human CD34⁺ peripheral blood hemopoietic progenitor cell-derived dendritic cells (DCs) with <i>Leishmania donovani</i> promastigotes, <i>Histoplasma capsulatum</i>, and <i>Mycobacterium kansasii</i> impairs the constitutive production of IL-12 from these cells. Thus, strategies aimed at modulating a dysregulated Th1/Th2 response to infection would be of great interest. To both augment the host immune response and deliver potent immunomodulatory cytokines such as IL-12 and IFN-γ, our goal is to develop a therapeutic strategy using genetically modified, microbial Ag-pulsed DCs. Toward developing such immunotherapies, we used retrovirus-mediated somatic gene transfer techniques to engineer human DCs to secrete biologically active IL-12 and IFN-γ. DCs pulsed with microbial antigens (e.g., leishmania and histoplasma Ags) were capable of inducing proliferative responses in autologous CD4⁺ lymphocytes. CD4⁺ lymphocytes cocultured with IL-12-transduced autologous DCs had enhanced Ag-specific proliferative responses compared with CD4⁺ lymphocytes cocultured with nontransduced or IFN-γ- transduced DCs. In this cell culture model system we demonstrate that IL-12 has a negative effect on IL-4 secretion that is independent of its ability to induce IFN-γ secretion. Taken together, these results indicate that IL-12-transduced DCs may be specifically suited in inducing or down-modulating Ag-specific Th1 or Th2 responses, respectively, and thus may be useful as adjunctive therapy in those intracellular infections in which a dominant Th1 response is critical for the resolution of infection." @default.
• W2035006354 created "2016-06-24" @default.
• W2035006354 creator A5082695396 @default.
• W2035006354 date "1990-05-01" @default.
• W2035006354 modified "2023-10-18" @default.
• W2035006354 title "Hypertrophic cardiomyopathy in the elderly." @default.
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• W2035006354 doi "https://doi.org/10.1136/hrt.63.5.265" @default.
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