TY - JOUR
T1 - 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
AU - Agaugué, Sophie
AU - Marcenaro, Emanuela
AU - Ferranti, Bruna
AU - Moretta, Lorenzo
AU - Moretta, Alessandro
PY - 2008/9/1
Y1 - 2008/9/1
N2 - Dendritic cells (DCs) play a crucial role in naive T-cell priming. Recent data suggested that natural killer (NK) cells can influence the capability of DCs to promote 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 interleukin (IL)-12, IL-2, or IL-18, promote distinct pathways of Th1 priming. IL-12- or IL-2-conditioned NK cells induce maturation of DCs capable of priming IFN-γ-producing Th1 cells. On the other hand, IL-18-conditioned NK cells induce Th1 polarization only when cocultured with both DCs and T cells. In this case, IL-2 released by T cells and IL-12 derived from DCs during the priming process promote interferon (IFN)-γ production. In contrast, when NK cells are exposed to IL-4, nonpolarized 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 DCs, leading to different outcomes in naive T-cell polarization.
AB - Dendritic cells (DCs) play a crucial role in naive T-cell priming. Recent data suggested that natural killer (NK) cells can influence the capability of DCs to promote 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 interleukin (IL)-12, IL-2, or IL-18, promote distinct pathways of Th1 priming. IL-12- or IL-2-conditioned NK cells induce maturation of DCs capable of priming IFN-γ-producing Th1 cells. On the other hand, IL-18-conditioned NK cells induce Th1 polarization only when cocultured with both DCs and T cells. In this case, IL-2 released by T cells and IL-12 derived from DCs during the priming process promote interferon (IFN)-γ production. In contrast, when NK cells are exposed to IL-4, nonpolarized 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 DCs, leading to different outcomes in naive T-cell polarization.
UR - http://www.scopus.com/inward/record.url?scp=52649116495&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=52649116495&partnerID=8YFLogxK
U2 - 10.1182/blood-2008-02-135871
DO - 10.1182/blood-2008-02-135871
M3 - Article
C2 - 18579793
AN - SCOPUS:52649116495
VL - 112
SP - 1776
EP - 1783
JO - Blood
JF - Blood
SN - 0006-4971
IS - 5
ER -