FUNCTIONAL ACTIVITY OF IFNα- AND IL-4-INDUCED HUMAN DENDRITIC CELLS: A COMPARATIVE STUDY

Abstract

We have performed a comparative analysis of allostimulatory, Th1/Th2-stimulatory and tolerogenic activities of dendritic cells (DCs) derived from healthy donors (n = 52). The DCs were generated in vitro with IFN-alpha (IFN-DCs) or IL-4 (IL-4-DCs). It was shown that IL-4-DCs and IFN-DCs did not differ in their key functional characteristics, i.e., in their ability to stimulate proliferation of T-cells in response to alloantigens, and to induce generation of T-regulatory cells in mixed leukocyte culture. IFN- and IL-4-induced DCs possess similar ability of boosting T cells to produce Th1/proinflammatory (IFNγ, IL-2, IL-1β, TNFα, IL-12, IL-17) and Th2/antiinflammatory cytokines (IL-4, IL-6, IL-10, IL-13), growth factors (G-CSF, GM-CSF, IL-7) and chemokines (IL-8, MIP-1β). Nevertheless, IFN-DCs have more pronounced stimulatory effect upon Th1 and Th2 cells, thus manifesting as a significantly higher IFNγ, IL-5 and MIP-1β production. IFN-DCs were characterized by more prominent ability to activate Th1-cells, and by moderate Th2-stimulatory activity, which is absent in IL-4-DCs. These data strongly suggest that IFN-DCs may present a quite promising cellular tool for development of therapeutic vaccines aiming to induce/enhance the immune response.