Dendritic cell regulation of immune responses: a new role for interleukin 2 at the intersection of innate and adaptive immunity

Abstract

Dendritic cells are professional antigen-presenting cells able to initiate innate and adaptive immune responses against invading pathogens. In response to external stimuli dendritic cells undergo a complete genetic reprogramming that allows them to become, soon after activation, natural killer cell activators and subsequently T cell stimulators. The recent observation that dendritic cells produce interleukin 2 following microbial stimulation opens new possibilities for understanding the efficiency of dendritic cells in regulating immune system functions. This review discusses how dendritic cells control natural killer, T- and B-cell responses and the relevance of interleukin 2 in these processes.

Fig. 1. Schematic representation of the DC maturation process. Following a microbial encounter, immature DCs undergo actin cytoskelton rearrangements (which induce downregulation of the phagocytic activity) and increase the efficiency of antigen processing and presentation to prime T cells. Moreover, activated DCs express, with strictly defined kinetics, cytokines and chemokines for activation and control of innate and acquired immune responses. Among the cytokines produced by early activated DCs, IL-2 plays a key role. At early time points, it helps to activate NK cells (IL-2 pathway, see Figure 2). At later time points, when DCs have not yet reached the final stage of maturation and still express low levels of costimulatory molecules and peptide–MHC complexes at the cell surface, DC-derived IL-2 cooperates in the activation of T-cell responses (late adaptive response). The possibility that IL-2 can also act on DC in an autocrine fashion cannot be excluded.

Fig. 2. Two possible pathways for DC-mediated NK cell activation. In the IL-4 pathway, immature DCs become competent NK cell activators in the presence of IL-4. This process is bidirectional and requires cell-to-cell contact and soluble factors. In the IL-2 pathway, early microbial activated DCs, which are IL-2 producers, acquire the ability to stimulate NK cells. This process depends on IL-2 and membrane proteins.