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 andtolerogenic activities of dendritic cells (DCs) derived from healthy donors (n = 52). The DCs were generatedin vitro with IFN-alpha (IFN-DCs) or IL-4 (IL-4-DCs). It was shown that IL-4-DCs and IFN-DCs didnot differ in their key functional characteristics, i.e., in their ability to stimulate proliferation of T-cells inresponse to alloantigens, and to induce generation of T-regulatory cells in mixed leukocyte culture. IFN- andIL-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 pronouncedstimulatory effect upon Th1 and Th2 cells, thus manifesting as a significantly higher IFNγ, IL-5 and MIP-1βproduction. IFN-DCs were characterized by more prominent ability to activate Th1-cells, and by moderateTh2-stimulatory activity, which is absent in IL-4-DCs. These data strongly suggest that IFN-DCs may presenta quite promising cellular tool for development of therapeutic vaccines aiming to induce/enhance the immuneresponse.

Keywords

• dendritic cells
• allostimulatory activity
• th1-/th2-сytokines
• regulatory t-cells