Human CD141+ (BDCA-3)+ dendritic cells (DCs) represent a unique myeloid DC subset that cross-presents necrotic cell antigens
Tóm tắt
The characterization of human dendritic cell (DC) subsets is essential for the design of new vaccines. We report the first detailed functional analysis of the human CD141+ DC subset. CD141+ DCs are found in human lymph nodes, bone marrow, tonsil, and blood, and the latter proved to be the best source of highly purified cells for functional analysis. They are characterized by high expression of toll-like receptor 3, production of IL-12p70 and IFN-β, and superior capacity to induce T helper 1 cell responses, when compared with the more commonly studied CD1c+ DC subset. Polyinosine-polycytidylic acid (poly I:C)–activated CD141+ DCs have a superior capacity to cross-present soluble protein antigen (Ag) to CD8+ cytotoxic T lymphocytes than poly I:C–activated CD1c+ DCs. Importantly, CD141+ DCs, but not CD1c+ DCs, were endowed with the capacity to cross-present viral Ag after their uptake of necrotic virus-infected cells. These findings establish the CD141+ DC subset as an important functionally distinct human DC subtype with characteristics similar to those of the mouse CD8α+ DC subset. The data demonstrate a role for CD141+ DCs in the induction of cytotoxic T lymphocyte responses and suggest that they may be the most relevant targets for vaccination against cancers, viruses, and other pathogens.
Từ khóa
Tài liệu tham khảo
Alexander, 2008, Can type-1 responses against intracellular pathogens be T helper 2 cytokine dependent?, Microbes Infect., 10, 953, 10.1016/j.micinf.2008.07.038
Aliberti, 2003, Essential role for ICSBP in the in vivo development of murine CD8alpha + dendritic cells, Blood., 101, 305, 10.1182/blood-2002-04-1088
Angel, 2009, Distinctive localization of antigen-presenting cells in human lymph nodes, Blood., 113, 1257, 10.1182/blood-2008-06-165266
Arrode, 2000, Incoming human cytomegalovirus pp65 (UL83) contained in apoptotic infected fibroblasts is cross-presented to CD8(+) T cells by dendritic cells, J. Virol., 74, 10018, 10.1128/JVI.74.21.10018-10024.2000
Bedoui, 2009, Characterization of an immediate splenic precursor of CD8+ dendritic cells capable of inducing antiviral T cell responses, J. Immunol., 182, 4200, 10.4049/jimmunol.0802286
Bedoui, 2009, Cross-presentation of viral and self antigens by skin-derived CD103+ dendritic cells, Nat. Immunol., 10, 488, 10.1038/ni.1724
Bonifaz, 2004, In vivo targeting of antigens to maturing dendritic cells via the DEC-205 receptor improves T cell vaccination, J. Exp. Med., 199, 815, 10.1084/jem.20032220
Burgdorf, 2008, Endocytosis mechanisms and the cell biology of antigen presentation, Curr. Opin. Immunol., 20, 89, 10.1016/j.coi.2007.12.002
Caminschi, 2008, The dendritic cell subtype-restricted C-type lectin Clec9A is a target for vaccine enhancement, Blood., 112, 3264, 10.1182/blood-2008-05-155176
Cavassani, 2008, TLR3 is an endogenous sensor of tissue necrosis during acute inflammatory events, J. Exp. Med., 205, 2609, 10.1084/jem.20081370
den Haan, 2000, CD8+ but not CD8− dendritic cells cross-prime cytotoxic T cells in vivo, J. Exp. Med., 192, 1685, 10.1084/jem.192.12.1685
Dong, 2008, Signal regulatory protein alpha negatively regulates both TLR3 and cytoplasmic pathways in type I interferon induction, Mol. Immunol., 45, 3025, 10.1016/j.molimm.2008.03.012
Dudziak, 2007, Differential antigen processing by dendritic cell subsets in vivo, Science., 315, 107, 10.1126/science.1136080
Dzionek, 2000, BDCA-2, BDCA-3, and BDCA-4: three markers for distinct subsets of dendritic cells in human peripheral blood, J. Immunol., 165, 6037, 10.4049/jimmunol.165.11.6037
Edwards, 2003, Toll-like receptor expression in murine DC subsets: lack of TLR7 expression by CD8 alpha+ DC correlates with unresponsiveness to imidazoquinolines, Eur. J. Immunol., 33, 827, 10.1002/eji.200323797
Galibert, 2005, Nectin-like protein 2 defines a subset of T-cell zone dendritic cells and is a ligand for class-I-restricted T-cell-associated molecule, J. Biol. Chem., 280, 21955, 10.1074/jbc.M502095200
Hart, 1997, Dendritic cells: unique leukocyte populations which control the primary immune response, Blood., 90, 3245, 10.1182/blood.V90.9.3245
Hildner, 2008, Batf3 deficiency reveals a critical role for CD8alpha+ dendritic cells in cytotoxic T cell immunity, Science., 322, 1097, 10.1126/science.1164206
Hochrein, 2001, Differential production of IL-12, IFN-alpha, and IFN-gamma by mouse dendritic cell subsets, J. Immunol., 166, 5448, 10.4049/jimmunol.166.9.5448
Huysamen, 2008, CLEC9A is a novel activation C-type lectin-like receptor expressed on BDCA3+ dendritic cells and a subset of monocytes, J. Biol. Chem., 283, 16693, 10.1074/jbc.M709923200
Iyoda, 2002, The CD8+ dendritic cell subset selectively endocytoses dying cells in culture and in vivo, J. Exp. Med., 195, 1289, 10.1084/jem.20020161
Jefford, 2003, Functional comparison of DCs generated in vivo with Flt3 ligand or in vitro from blood monocytes: differential regulation of function by specific classes of physiologic stimuli, Blood., 102, 1753, 10.1182/blood-2002-12-3854
Kadowaki, 2001, Subsets of human dendritic cell precursors express different toll-like receptors and respond to different microbial antigens, J. Exp. Med., 194, 863, 10.1084/jem.194.6.863
Karikó, 2004, mRNA is an endogenous ligand for Toll-like receptor 3, J. Biol. Chem., 279, 12542, 10.1074/jbc.M310175200
Keller, 2010, Cutting edge: limited specialization of dendritic cell subsets for MHC class II-associated presentation of viral particles, J. Immunol., 184, 26, 10.4049/jimmunol.0901540
Kyte, 2009, Unconventional cytokine profiles and development of T cell memory in long-term survivors after cancer vaccination, Cancer Immunol. Immunother., 58, 1609, 10.1007/s00262-009-0670-2
Lahoud, 2006, Signal regulatory protein molecules are differentially expressed by CD8- dendritic cells, J. Immunol., 177, 372, 10.4049/jimmunol.177.1.372
Le Bon, 2008, Type I interferon as a stimulus for cross-priming, Cytokine Growth Factor Rev., 19, 33, 10.1016/j.cytogfr.2007.10.007
Lindell, 2008, CXCL10/CXCR3-mediated responses promote immunity to respiratory syncytial virus infection by augmenting dendritic cell and CD8(+) T cell efficacy, Eur. J. Immunol., 38, 2168, 10.1002/eji.200838155
Lindstedt, 2005, Gene family clustering identifies functionally associated subsets of human in vivo blood and tonsillar dendritic cells, J. Immunol., 175, 4839, 10.4049/jimmunol.175.8.4839
López-Bravo, 2008, In vivo induction of immune responses to pathogens by conventional dendritic cells, Immunity., 29, 343, 10.1016/j.immuni.2008.08.008
Luber, 2010, Quantitative proteomics reveals subset-specific viral recognition in dendritic cells, Immunity., 32, 279, 10.1016/j.immuni.2010.01.013
Luft, 2002, Functionally distinct dendritic cell (DC) populations induced by physiologic stimuli: prostaglandin E(2) regulates the migratory capacity of specific DC subsets, Blood., 100, 1362, 10.1182/blood-2001-12-0360
Lundie, 2008, Blood-stage Plasmodium infection induces CD8+ T lymphocytes to parasite-expressed antigens, largely regulated by CD8alpha+ dendritic cells, Proc. Natl. Acad. Sci. USA., 105, 14509, 10.1073/pnas.0806727105
MacDonald, 2002, Characterization of human blood dendritic cell subsets, Blood., 100, 4512, 10.1182/blood-2001-11-0097
Mailliard, 2004, alpha-type-1 polarized dendritic cells: a novel immunization tool with optimized CTL-inducing activity, Cancer Res., 64, 5934, 10.1158/0008-5472.CAN-04-1261
Maldonado-López, 1999, CD8α+ and CD8α− subclasses of dendritic cells direct the development of distinct T helper cells in vivo, J. Exp. Med., 189, 587, 10.1084/jem.189.3.587
Matsumoto, 2003, Subcellular localization of Toll-like receptor 3 in human dendritic cells, J. Immunol., 171, 3154, 10.4049/jimmunol.171.6.3154
Naik, 2008, Demystifying the development of dendritic cell subtypes, a little, Immunol. Cell Biol., 86, 439, 10.1038/icb.2008.28
Nakhaei, 2009, RIG-I-like receptors: sensing and responding to RNA virus infection, Semin. Immunol., 21, 215, 10.1016/j.smim.2009.05.001
O’Keeffe, 2003, Dendritic cell precursor populations of mouse blood: identification of the murine homologues of human blood plasmacytoid pre-DC2 and CD11c+ DC1 precursors, Blood., 101, 1453, 10.1182/blood-2002-03-0974
Orabona, 2006, Toward the identification of a tolerogenic signature in IDO-competent dendritic cells, Blood., 107, 2846, 10.1182/blood-2005-10-4077
Piccioli, 2007, Functional specialization of human circulating CD16 and CD1c myeloid dendritic-cell subsets, Blood., 109, 5371, 10.1182/blood-2006-08-038422
Poeck, 2010, Recognition of RNA virus by RIG-I results in activation of CARD9 and inflammasome signaling for interleukin 1 beta production, Nat. Immunol., 11, 63, 10.1038/ni.1824
Pooley, 2001, Cutting edge: intravenous soluble antigen is presented to CD4 T cells by CD8- dendritic cells, but cross-presented to CD8 T cells by CD8+ dendritic cells, J. Immunol., 166, 5327, 10.4049/jimmunol.166.9.5327
Pulendran, 1999, Distinct dendritic cell subsets differentially regulate the class of immune response in vivo, Proc. Natl. Acad. Sci. USA., 96, 1036, 10.1073/pnas.96.3.1036
Radford, 2006, CD11c+ blood dendritic cells induce antigen-specific cytotoxic T lymphocytes with similar efficiency compared to monocyte-derived dendritic cells despite higher levels of MHC class I expression, J. Immunother., 29, 596, 10.1097/01.cji.0000211310.90621.5d
Reis e Sousa, 1997, In vivo microbial stimulation induces rapid CD40 ligand-independent production of interleukin 12 by dendritic cells and their redistribution to T cell areas, J. Exp. Med., 186, 1819, 10.1084/jem.186.11.1819
Robbins, 2008, Novel insights into the relationships between dendritic cell subsets in human and mouse revealed by genome-wide expression profiling, Genome Biol., 9, R17, 10.1186/gb-2008-9-1-r17
Rudd, 2005, Differential role for TLR3 in respiratory syncytial virus-induced chemokine expression, J. Virol., 79, 3350, 10.1128/JVI.79.6.3350-3357.2005
Sancho, 2008, Tumor therapy in mice via antigen targeting to a novel, DC-restricted C-type lectin, J. Clin. Invest., 118, 2098, 10.1172/JCI34584
Sancho, 2009, Identification of a dendritic cell receptor that couples sensing of necrosis to immunity, Nature., 458, 899, 10.1038/nature07750
Scheu, 2008, Visualization of IFNbeta production by plasmacytoid versus conventional dendritic cells under specific stimulation conditions in vivo, Proc. Natl. Acad. Sci. USA., 105, 20416, 10.1073/pnas.0808537105
Schiavoni, 2002, ICSBP is essential for the development of mouse type I interferon-producing cells and for the generation and activation of CD8α+ dendritic cells, J. Exp. Med., 196, 1415, 10.1084/jem.20021263
Schnorrer, 2006, The dominant role of CD8+ dendritic cells in cross-presentation is not dictated by antigen capture, Proc. Natl. Acad. Sci. USA., 103, 10729, 10.1073/pnas.0601956103
Schnurr, 2005, Tumor antigen processing and presentation depend critically on dendritic cell type and the mode of antigen delivery, Blood., 105, 2465, 10.1182/blood-2004-08-3105
Schulz, 2005, Toll-like receptor 3 promotes cross-priming to virus-infected cells, Nature., 433, 887, 10.1038/nature03326
Skokos, 2007, CD8− DCs induce IL-12–independent Th1 differentiation through Delta 4 Notch-like ligand in response to bacterial LPS, J. Exp. Med., 204, 1525, 10.1084/jem.20062305
Soares, 2007, A subset of dendritic cells induces CD4+ T cells to produce IFN-γ by an IL-12–independent but CD70-dependent mechanism in vivo, J. Exp. Med., 204, 1095, 10.1084/jem.20070176
Steinman, 2008, Dendritic cells in vivo: a key target for a new vaccine science, Immunity., 29, 319, 10.1016/j.immuni.2008.08.001
Stoitzner, 2006, Langerhans cells cross-present antigen derived from skin, Proc. Natl. Acad. Sci. USA., 103, 7783, 10.1073/pnas.0509307103
Urban, 2006, The frequency of BDCA3-positive dendritic cells is increased in the peripheral circulation of Kenyan children with severe malaria, Infect. Immun., 74, 6700, 10.1128/IAI.00861-06
Velásquez-Lopera, 2008, Human spleen contains different subsets of dendritic cells and regulatory T lymphocytes, Clin. Exp. Immunol., 154, 107, 10.1111/j.1365-2249.2008.03734.x
Villadangos, 2007, Intrinsic and cooperative antigen-presenting functions of dendritic-cell subsets in vivo, Nat. Rev. Immunol., 7, 543, 10.1038/nri2103
Vulink, 2008, Dendritic cells in cancer immunotherapy, Adv. Cancer Res., 99, 363, 10.1016/S0065-230X(07)99006-5