PMID- 18820727 OWN - NLM STAT- MEDLINE DCOM- 20081125 LR - 20181113 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 3 IP - 9 DP - 2008 Sep 29 TI - Quantum dots for tracking dendritic cells and priming an immune response in vitro and in vivo. PG - e3290 LID - 10.1371/journal.pone.0003290 [doi] LID - e3290 AB - Dendritic cells (DCs) play a key role in initiating adaptive immune response by presenting antigen to T cells in lymphoid organs. Here, we investigate the potential of quantum dots (QDs) as fluorescent nanoparticles for in vitro and in vivo imaging of DCs, and as a particle-based antigen-delivery system to enhance DC-mediated immune responses. We used confocal, two-photon, and electron microscopies to visualize QD uptake into DCs and compared CD69 expression, T cell proliferation, and IFN-gamma production by DO11.10 and OT-II T cells in vivo in response to free antigen or antigen-conjugated to QDs. CD11c(+) DCs avidly and preferentially endocytosed QDs, initially into small vesicles near the plasma membrane by an actin-dependent mechanism. Within 10 min DCs contained vesicles of varying size, motion, and brightness distributed throughout the cytoplasm. At later times, endocytosed QDs were compartmentalized inside lysosomes. LPS-induced maturation of DCs reduced the rate of endocytosis and the proportion of cells taking up QDs. Following subcutaneous injection of QDs in an adjuvant depot, DCs that had endocytosed QDs were visualized up to 400 microm deep within draining lymph nodes. When antigen-conjugated QDs were used, T cells formed stable clusters in contact with DCs. Antigen-conjugated QDs induced CD69 expression, T cell proliferation, and IFN-gamma production in vivo with greater efficiency than equivalent amounts of free antigen. These results establish QDs as a versatile platform for immunoimaging of dendritic cells and as an efficient nanoparticle-based antigen delivery system for priming an immune response. FAU - Sen, Debasish AU - Sen D AD - Department of Physiology and Biophysics, University of California Irvine, Irvine, California, United States of America. FAU - Deerinck, Thomas J AU - Deerinck TJ FAU - Ellisman, Mark H AU - Ellisman MH FAU - Parker, Ian AU - Parker I FAU - Cahalan, Michael D AU - Cahalan MD LA - eng GR - GM-41514/GM/NIGMS NIH HHS/United States GR - R01 GM048071/GM/NIGMS NIH HHS/United States GR - R37 GM048071/GM/NIGMS NIH HHS/United States GR - N01AI50019/AI/NIAID NIH HHS/United States GR - GM-48071/GM/NIGMS NIH HHS/United States GR - R01 GM041514/GM/NIGMS NIH HHS/United States GR - P30 CA062203/CA/NCI NIH HHS/United States GR - N01-AI-50019/AI/NIAID NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20080929 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 82115-62-6 (Interferon-gamma) SB - IM MH - Animals MH - Cell Proliferation MH - Dendritic Cells/cytology/*physiology MH - Endocytosis MH - Immune System/cytology/*physiology MH - In Vitro Techniques MH - Interferon-gamma/metabolism MH - Kinetics MH - Mice MH - Mice, Inbred BALB C MH - Mice, Inbred C57BL MH - Microscopy, Confocal MH - Microscopy, Electron MH - Models, Biological MH - *Quantum Dots MH - T-Lymphocytes/immunology PMC - PMC2538605 COIS- Competing Interests: The authors have declared that no competing interests exist. EDAT- 2008/09/30 09:00 MHDA- 2008/12/17 09:00 PMCR- 2008/09/29 CRDT- 2008/09/30 09:00 PHST- 2008/06/03 00:00 [received] PHST- 2008/09/05 00:00 [accepted] PHST- 2008/09/30 09:00 [pubmed] PHST- 2008/12/17 09:00 [medline] PHST- 2008/09/30 09:00 [entrez] PHST- 2008/09/29 00:00 [pmc-release] AID - 08-PONE-RA-04947R1 [pii] AID - 10.1371/journal.pone.0003290 [doi] PST - epublish SO - PLoS One. 2008 Sep 29;3(9):e3290. doi: 10.1371/journal.pone.0003290.