Submitted February 19, 2008
Accepted June 4, 2008
Human natural killer cells exposed to IL-2, IL-12, IL-18 or IL-4 differently modulate priming of naive T cells by monocyte-derived dendritic cells
Sophie Agaugue, Emanuela Marcenaro, Bruna Ferranti, Lorenzo Moretta, and Alessandro Moretta*
Department of Experimental Medicine-Histology, University of Genova, Genova, Italy
Istituto G. Gaslini, Gaslini Hospital, Genova, Italy
Centro di Eccellenza per le Ricerche Biomediche, University of Genova, Genova, Italy
* Corresponding author; email: alemoret{at}unige.it.
Dendritic cells (DC) play a crucial role in naive T cell priming. Recent data suggested that NK cells can influence the capability of DC of promoting Th1 polarization. This regulatory function is primarily mediated by cytokines released in the microenvironment during inflammatory responses involving NK cells. In this study, we show that human NK cells exposed for short time to IL-12, IL-2 or IL-18, promote distinct pathways of Th1 priming. IL-12 or IL-2-conditioned NK cells induce maturation of DC capable of priming IFN-gamma-producing Th1 cells. On the other hand, IL-18-conditioned NK cells induce Th1 polarization only when co-cultured with both DC and T cells. In this case, IL-2 released by T cells and IL-12 derived from DC during the priming process promote IFN-gamma production. In contrast, when NK cells are exposed to IL-4, non polarized T cells releasing only low levels of IL-2 are generated. Thus, the prevalence of IL-12, IL-2, IL-18 or IL-4 at inflammatory sites may differentially modulate the NK cell interaction with DC leading to different outcomes in naive T cell polarization.
