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      Antigen Presenting Properties of a Myeloid Dendritic-Like Cell in Murine Spleen

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      PLoS ONE
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          Abstract

          This paper distinguishes a rare subset of myeloid dendritic-like cells found in mouse spleen from conventional (c) dendritic cells (DC) in terms of phenotype, function and gene expression. These cells are tentatively named “L-DC” since they resemble dendritic-like cells produced in longterm cultures of spleen. L-DC can be distinguished on the basis of their unique phenotype as CD11b hiCD11c loMHCII -CD43 +Ly6C -Ly6G -Siglec-F - cells. They demonstrate similar ability as cDC to uptake and retain complex antigens like mannan via mannose receptors, but much lower ability to endocytose and retain soluble antigen. While L-DC differ from cDC by their inability to activate CD4 + T cells, they are capable of antigen cross-presentation for activation of CD8 + T cells, although less effectively so than the cDC subsets. In terms of gene expression, CD8 - cDC and CD8 + cDC are quite distinct from L-DC. CD8 + cDC are distinguishable from the other two subsets by expression of CD24a, Clec9a, Xcr1 and Tlr11, while CD8 - cDC are distinguished by expression of Ccnd1 and H-2Eb2. L-DC are distinct from the two cDC subsets through upregulated expression of Clec4a3, Emr4, Itgam, Csf1r and CD300ld. The L-DC gene profile is quite distinct from that of cDC, confirming a myeloid cell type with distinct antigen presenting properties.

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          Most cited references56

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          Differential antigen processing by dendritic cell subsets in vivo.

          Dendritic cells (DCs) process and present self and foreign antigens to induce tolerance or immunity. In vitro models suggest that induction of immunity is controlled by regulating the presentation of antigen, but little is known about how DCs control antigen presentation in vivo. To examine antigen processing and presentation in vivo, we specifically targeted antigens to two major subsets of DCs by using chimeric monoclonal antibodies. Unlike CD8+ DCs that express the cell surface protein CD205, CD8- DCs, which are positive for the 33D1 antigen, are specialized for presentation on major histocompatibility complex (MHC) class II. This difference in antigen processing is intrinsic to the DC subsets and is associated with increased expression of proteins involved in MHC processing.
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            Cd8+ but Not Cd8− Dendritic Cells Cross-Prime Cytotoxic T Cells in Vivo

            Bone marrow–derived antigen-presenting cells (APCs) take up cell-associated antigens and present them in the context of major histocompatibility complex (MHC) class I molecules to CD8+ T cells in a process referred to as cross-priming. Cross-priming is essential for the induction of CD8+ T cell responses directed towards antigens not expressed in professional APCs. Although in vitro experiments have shown that dendritic cells (DCs) and macrophages are capable of presenting exogenous antigens in association with MHC class I, the cross-presenting cell in vivo has not been identified. We have isolated splenic DCs after in vivo priming with ovalbumin-loaded β2-microglobulin–deficient splenocytes and show that they indeed present cell-associated antigens in the context of MHC class I molecules. This process is transporter associated with antigen presentation (TAP) dependent, suggesting an endosome to cytosol transport. To determine whether a specific subset of splenic DCs is involved in this cross-presentation, we negatively and positively selected for CD8− and CD8+ DCs. Only the CD8+, and not the CD8−, DC subset demonstrates cross-priming ability. FACS® studies after injection of splenocytes loaded with fluorescent beads showed that 1 and 0.6% of the CD8+ and the CD8− DC subsets, respectively, had one or more associated beads. These results indicate that CD8+ DCs play an important role in the generation of cytotoxic T lymphocyte responses specific for cell-associated antigens.
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              Cytochrome C-mediated apoptosis.

              Apoptosis, or programmed cell death, is involved in development, elimination of damaged cells, and maintenance of cell homeostasis. Deregulation of apoptosis may cause diseases, such as cancers, immune diseases, and neurodegenerative disorders. Apoptosis is executed by a subfamily of cysteine proteases known as caspases. In mammalian cells, a major caspase activation pathway is the cytochrome c-initiated pathway. In this pathway, a variety of apoptotic stimuli cause cytochrome c release from mitochondria, which in turn induces a series of biochemical reactions that result in caspase activation and subsequent cell death. In this review, we focus on the recent progress in understanding the biochemical mechanisms and regulation of the pathway, the roles of the pathway in physiology and disease, and their potential therapeutic values.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                21 September 2016
                2016
                : 11
                : 9
                : e0162358
                Affiliations
                [1 ]Research School of Biology, Australian National University, Canberra, ACT, Australia
                [2 ]Clem Jones Research Centre for Regenerative Medicine, Bond University, Gold Coast, Queensland, Australia
                INSERM, FRANCE
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                • Conceptualization: YH HO.

                • Data curation: YH.

                • Formal analysis: YH.

                • Funding acquisition: HO.

                • Investigation: YH.

                • Methodology: YH HO.

                • Project administration: HO.

                • Resources: YH HO.

                • Supervision: HO.

                • Validation: YH HO.

                • Writing – original draft: YH HO.

                • Writing – review & editing: YH HO.

                Article
                PONE-D-16-11806
                10.1371/journal.pone.0162358
                5031434
                27654936
                532ca7e0-3f8f-452f-96ad-3f5a3d9233d2
                © 2016 Hey, O’Neill

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 1 April 2016
                : 22 August 2016
                Page count
                Figures: 7, Tables: 0, Pages: 23
                Funding
                Funded by: funder-id http://dx.doi.org/10.13039/501100000925, National Health and Medical Research Council;
                Award ID: 585443
                Award Recipient : Helen C. ONeill
                This work was supported by funding from the National Health and Medical Research Council of Australia to H.O (Project grant # 585443 ( https://www.nhmrc.gov.au/). Y.H. was supported by an Australian National University Graduate School scholarship. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Biology and life sciences
                Cell biology
                Cellular types
                Animal cells
                Blood cells
                White blood cells
                T cells
                Cytotoxic T cells
                Biology and life sciences
                Cell biology
                Cellular types
                Animal cells
                Immune cells
                White blood cells
                T cells
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                Biology and life sciences
                Immunology
                Immune cells
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                Medicine and health sciences
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                Spleen
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