Expression of CCR-7, MIP-3 beta, and Th-1 chemokines in type IIFN-induced monocyte-derived dendritic cells: importance for the rapid acquisition of potent migratory and functional activities

The migration capability of dendritic cells (DCs) is regulated by their res ponse to factors, namely chemokines, that characterize maturation stage and shape their functional activities. This study examines the morphology, exp ression of chemokines/chemokine receptors, and migration properties of DCs generated after treatment of monocytes with type I interferon (IFN) and gra nulocyte-macrophage colony-stimulating factor (GM-CSF) (IFN-DCs). IFN-DCs s howed phenotypical and morphologic features undetectable in DCs generated i n the presence of interleukin 4 (IL-4) and GM-CSF, such as expression of CD 83 and CD25 and the presence of CD44(+), highly polarized, thin, and long d endrites. IFN-DCs markedly migrated in response to beta -chemokines (especi ally MIP-1 beta) and expressed the Th-1 chemokine IP-10. Notably, IFN-DCs s howed an up-regulation of CCR7 as well as of its natural ligand MIP-3 beta, characteristics typical of mature DCs. Of interest, IFN-DCs exhibited a ma rked chemotactic response to MIP-3 beta in vitro and strong migratory behav ior in severe combined immunodeficient (SCID) mice. In SCID mice reconstitu ted with human peripheral blood leukocytes, IFN-DCs induced a potent primar y human antibody response and IFN-T production, indicative of a Th-1 immune response. These results define the highly specialized maturation state of IFN-DCs and point out the existence of a "natural alliance" between type I IFN and monocyte/DC development, instrumental for ensuring an efficient con nection between innate and adaptive immunity. (C) 2001 by The American Soci ety of Hematology.