PMID- 18579793 OWN - NLM STAT- MEDLINE DCOM- 20080930 LR - 20210206 IS - 1528-0020 (Electronic) IS - 0006-4971 (Linking) VI - 112 IP - 5 DP - 2008 Sep 1 TI - 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. PG - 1776-83 LID - 10.1182/blood-2008-02-135871 [doi] 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-gamma-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)-gamma 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. FAU - Agaugue, Sophie AU - Agaugue S AD - Dipartimento di Medicina Sperimentale, Universita degli Studi di Genova, Italy. FAU - Marcenaro, Emanuela AU - Marcenaro E FAU - Ferranti, Bruna AU - Ferranti B FAU - Moretta, Lorenzo AU - Moretta L FAU - Moretta, Alessandro AU - Moretta A LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20080625 PL - United States TA - Blood JT - Blood JID - 7603509 RN - 0 (Culture Media, Conditioned) RN - 0 (IL2 protein, human) RN - 0 (IL4 protein, human) RN - 0 (Inflammation Mediators) RN - 0 (Interleukin-18) RN - 0 (Interleukin-2) RN - 0 (Interleukins) RN - 187348-17-0 (Interleukin-12) RN - 207137-56-2 (Interleukin-4) SB - IM MH - Cell Communication MH - Cell Differentiation MH - Cells, Cultured MH - Coculture Techniques MH - Culture Media, Conditioned MH - Dendritic Cells/cytology/*immunology MH - Humans MH - Inflammation Mediators/metabolism MH - Interleukin-12/pharmacology MH - Interleukin-18/pharmacology MH - Interleukin-2/pharmacology MH - Interleukin-4/pharmacology MH - Interleukins/metabolism/*pharmacology MH - Killer Cells, Natural/*drug effects/*immunology MH - Monocytes/cytology/immunology MH - T-Lymphocytes/cytology/*immunology MH - Th1 Cells/cytology/immunology EDAT- 2008/06/27 09:00 MHDA- 2008/10/01 09:00 CRDT- 2008/06/27 09:00 PHST- 2008/06/27 09:00 [pubmed] PHST- 2008/10/01 09:00 [medline] PHST- 2008/06/27 09:00 [entrez] AID - S0006-4971(20)49611-9 [pii] AID - 10.1182/blood-2008-02-135871 [doi] PST - ppublish SO - Blood. 2008 Sep 1;112(5):1776-83. doi: 10.1182/blood-2008-02-135871. Epub 2008 Jun 25.