DOCSLIB.ORG

Dendritic/Monocytic APC Discriminates Differentiation Stages

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Dendritic/Monocytic APC Discriminates Differentiation Stages HLA-DR-Mediated Apoptosis Susceptibility Discriminates Differentiation Stages of Dendritic/Monocytic APC1 Nicolas Bertho,* Bernard Dre´nou,* Be´atrice Laupeze,* Claudine Le Berre,† Laurence Amiot,* Jean-Marc Grosset,* Olivier Fardel,‡ Dominique Charron,§ Nuala Mooney,2§ and Rene´e Fauchet* Professional APC are characterized by their ability to present peptide via HLA class II in the presence of costimulatory molecules (CD40, CD80, and CD86). The efficiency of Ag presentation can be classed as follows: mature dendritic cells (DC) are most efficient, immature DC and macrophages are intermediate, and monocytes are considered poor APC. There is a large body of evidence demonstrating that HLA-DR transmits signals in the APC. In this study, we have addressed the question of the outcome of HLA-DR signals on APC of the monocyte/DC lineages throughout their differentiation from immature to mature APC. DC were .generated from both monocytes and CD34؉ cells of the same individual, macrophages were differentiated from monocytes Immunophenotypical analysis clearly distinguished these populations. HLA-DR-mediated signals led to marked apoptosis in mature DC of either CD34 or monocytic origin. Significantly less apoptosis was observed in immature DC of either origin. Nonetheless, even immature DC were more susceptible to HLA-DR-mediated apoptosis than macrophages, whereas monocytes were resistant to HLA-DR-mediated apoptosis. The mechanism of HLA-DR-mediated apoptosis was independent of caspase activation. Taken together, these data lead to the notion that signals generated via HLA-DR lead to the demise of mature professional APC, thereby providing a means of limiting the immune response. The Journal of Immunology, 2000, 164: 2379– 2385. rofessional APC represent a subset responsible for thymic membrane ligands (CD40-L), they migrate from tissues to periph- selection and peripheral T cell activation (1). Ag-specific eral lymph nodes. In the course of their migration, they undergo P immune responses of CD4 T cells depends on the success- maturation and are considered mature when localized in lymph ful presentation of processed peptide Ags by HLA class II mole- nodes. Mature DC express CD83 (6) and have enhanced HLA cules (HLA-DR, -DP, and -DQ) (2). These molecules are consti- class I, class II, CD80, and CD86 expression (7). Immature DC can tutively expressed on professional APC including dendritic cells be generated in vitro from either peripheral blood monocytes (8) 3 (DC) (3), macrophages, and B lymphocytes. using GM-CSF and IL-4 or from CD34ϩ hemopoietic stem cells DC are the most potent APC (reviewed in Ref. 4), with the (9) using GM-CSF and TNF-␣. Maturation of cultured immature unique ability to prime naive T cells (5). Tissular DC are consid- DC may be obtained by a 48-h incubation with TNF-␣, bacterial ered as immature and can be identified by their expression of HLA LPS (10), or CD40-L (11). DC differentiation and maturation can class I and II molecules, CD1a, CD40, CD80 (B7.1), and CD86 therefore be reproduced in vitro. The success of Ag presentation by (B7.2) but not CD83. They capture and process Ag with high DC has led to them being considered as promising tools for im- efficiency. When DC receive inflammation signals mediated by munotherapy (12, 13). chemokines (macrophage-inflammatory protein 3␣, macrophage- Macrophages express HLA class I and HLA class II Ags as well inflammatory protein 1␣, and RANTES) and cytokines (TNF-␣)or as CD80 and CD86 accessory molecules (14). They are character- ized by their high ability to phagocytose, which allows them *Laboratoire Universitaire d’He´matologie et de Biologie des Cellules Sanguines, In- to process and to present particulate Ags. However, macrophages stitut National de la Sante´ et de la Recherche Me´dicale CRI 9606-UPRES EA 22-33, are less effective than DC in Ag presentation to T lymphocytes † Rennes, France; Etablissement de Transfusion Sanguine de Bretagne, Rennes, (15, 16). France; ‡Institut National de la Sante´ et de la Recherche Me´dicale U456 Universite´de Rennes I, Rennes, France; and §Institut National de la Sante´ et de la Recherche B lymphocytes are considered to be professional APC (17) and Me´dicale U396 Institut des Cordeliers, Paris, France express the requisite accessory molecules for T lymphocyte acti- Received for publication July 12, 1999. Accepted for publication December 20, 1999. vation (such as CD86, CD80, and CD40 molecules (18)) as well as The costs of publication of this article were defrayed in part by the payment of page HLA class II molecules. There is ample evidence for HLA-DR- charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. mediated signal transduction in B lymphocytes (reviewed in Ref. ␤ 1 This work was supported by grants from the Agence Franc¸aise du Sang. N.B. is a 19). The intracytoplasmic region of the HLA-DR -chain is crit- recipient of a fellowship from Rennes I University. B.L. is a recipient of a fellowship ical for the translocation of protein kinase C ␣ and ␤II (20). Con- from la Ligue contre le cancer (Comite´ des Coˆtes d’Armor). We are grateful for the sequences of these signals are either proliferation and differentia- financial support of Association pour la Recherche sur le Cancer, La Ligue Contre le Cancer (LLCLC), and LLCLC (Comite´ de Paris), EC grants B70-4-98-0458 and tion (21), cell-cell adhesion (22), or cell death (23). Activated ESF-IGA. human B lymphocytes are more susceptible to HLA-DR-mediated 2 Address correspondence and reprint requests to Dr. Nuala Mooney, Laboratoire apoptosis than resting cells (24, 25). The mechanism of HLA-DR- d’Immunoge´ne´tique Humaine, Institut Biome´dical des Cordeliers, 15 rue de l’e´cole de me´decine/Bat A, 75006 Paris, France. mediated cell death has not been elucidated, although enhancement 3 Abbreviations used in this paper: DC, dendritic cell; SCF, stem cell factor; L, ligand; of sensitivity to CD95/Fas (26) and expression of Fas-L (27) has PI, propidium iodide. been described after HLA-DR cross-linking. Fas, in common with Copyright © 2000 by The American Association of Immunologists 0022-1767/00/$02.00 2380 PROFESSIONAL APC ARE TARGETS FOR HLA-DR-MEDIATED APOPTOSIS other death receptors, initiates activation of cysteinyl aspartate- were composed of 84.5 Ϯ 5.8% CD14ϩ cells when analyzed by flow cy- ϩ specific proteinases (caspases) which are considered as the prin- tometry. Nonadherent cells were removed for isolation of CD34 cells. Nonadherent cells were allowed to adhere for another 30 min in 45-cm2 cipal executioners of Fas-induced apoptosis (28, 29). ϩ flasks to remove remaining monocytes before isolation of CD34 cells. Ag presentation needs TCR and CD4 interaction with HLA Hemopoietic progenitors were positively selected using CD34-conjugated class II molecules but also activation of cells by costimulation immunomagnetic beads (Dynabeads M-450 CD34; Dynal, Oslo, Norway) molecules (30). Numerous mechanisms to control the T cell re- according to the manufacturer’s instructions. The final purity of CD34ϩ sponse have been described (anergy, apoptosis). Mechanisms con- cells was 88.9% Ϯ 5.7% as demonstrated by flow cytometry analysis. trolling the APC response have not yet been elucidated. Since Generation of DC and macrophages HLA-DR mediated more cell death in activated than in resting B cells, it has been postulated to play a role in the termination of the Macrophages. Monocytes (adherent cells) were cultured for 7 days in immune response (23). If this were the case, HLA-DR-mediated IMDM (Life Technologies) and 10% FCS supplemented with 800 U/ml GM-CSF. Cultures were fed by replacing half of the medium at day 3. cell death could be also expected to occur in other APC. Tyrosine Monocyte-derived DC. Adherent cells were cultured in IMDM, 10% protein kinase activation via HLA-DR on DC has been reported FCS supplemented with 800 U/ml GM-CSF, and 1000 U/ml IL-4. Half of (31); however, the question of apoptosis has not been addressed. the medium was replaced at days 3, 5, and 7 by fresh medium with 800 We have examined the role of HLA-DR-mediated signals U/ml GM-CSF and 500 U/ml IL-4. At day 7, 100 U/ml TNF-␣ was added to culture to provided mature monocyte-derived DC. throughout differentiation of primary professional APC. Hemopoi- ؉ etic progenitors, monocytes, macrophages, as well as immature Hemopoietic progenitor (CD34 cells)-derived DC. Isolated CD34ϩ cells were cultured in IMDM, 10% FCS supplemented with 500 and mature DC were examined. We have compared DC derived ␣ ϩ U/ml GM-CSF, 2.5 U/ml SCF, 10 U/ml Flt3-L, and 200 U/ml TNF- . from both monocytes and CD34 cells of the same individual to Cultures were fed by replacing half of the culture medium by fresh medium ensure that the results obtained were representative of DC regard- at days 5, 9, and 14. At day 14, 100 ng/ml LPS was added to provide less of their origin. We report HLA-DR-mediated apoptosis of mature CD34-derived DC. mature differentiated APC which did not appear to depend on Phenotypic analysis of cells by flow cytometry caspase activation. An in vitro model of APC differentiation and maturation allowed us to demonstrate that the apoptotic function of Before labeling, cells were incubated for1hinhuman AB serum, at 4°C, MHC class II is differentially regulated in professional APC sub- to avoid nonspecific mAb binding. Several mAbs were used for immuno- labeling: FITC- or PE-conjugated mouse mAb against CD1a, CD14, CD34, sets. Finally, these results strongly suggest an “autoregulation” of and HLA-DR, and FITC-labeled isotype controls were purchased from MHC class II-mediated Ag presentation.
Load more

Recommended publications
  • Inhibition of Midkine Alleviates Experimental Autoimmune Encephalomyelitis Through the Expansion of Regulatory T Cell Population
    Inhibition of midkine alleviates experimental autoimmune encephalomyelitis through the expansion of regulatory T cell population Jinyan Wang*, Hideyuki Takeuchi*†, Yoshifumi Sonobe*, Shijie Jin*, Tetsuya Mizuno*, Shin Miyakawa‡, Masatoshi Fujiwara‡, Yoshikazu Nakamura§¶, Takuma Katoʈ, Hisako Muramatsu**, Takashi Muramatsu**††, and Akio Suzumura*† *Department of Neuroimmunology, Research Institute of Environmental Medicine, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8601, Japan; ‡RIBOMIC, Inc., 3-15-5-601 Shirokanedai, Minato-ku, Tokyo 108-0071, Japan; §Department of Basic Medical Sciences, Institute of Medical Science, University of Tokyo, Shirokanedai, Minato-ku, Tokyo 108-8639, Japan; ¶Core Research Evolutional Science and Technology, Japan Science and Technology Agency, Toyonaka, Osaka 560-8531, Japan; ʈDepartment of Bioregulation, Mie University Graduate School of Medicine, Tsu, Mie 514-8507, Japan; **Department of Biochemistry, Nagoya University Graduate School of Medicine, Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan; and ††Department of Health Science, Faculty of Psychological and Physical Sciences, Aichi Gakuin University, Nisshin, Aichi 470-0195, Japan Edited by Ethan Shevach, National Institutes of Health, Bethesda, MD, and accepted by the Editorial Board January 20, 2008 (received for review October 12, 2007) CD4؉CD25؉ regulatory T (Treg) cells are crucial mediators of nity, and abnormalities in Treg cell function may contribute to the autoimmune tolerance. The factors that regulate Treg cells, how- development of
    [Show full text]
  • Immunomodulation and Generation of Tolerogenic Dendritic Cells by Probiotic Bacteria in Patients with Inflammatory Bowel Disease
    International Journal of Molecular Sciences Article Immunomodulation and Generation of Tolerogenic Dendritic Cells by Probiotic Bacteria in Patients with Inflammatory Bowel Disease 1, 2, 1 Shaghayegh Baradaran Ghavami y, Abbas Yadegar y , Hamid Asadzadeh Aghdaei , Dario Sorrentino 3,4,*, Maryam Farmani 1 , Adil Shamim Mir 5, Masoumeh Azimirad 2 , Hedieh Balaii 6, Shabnam Shahrokh 6 and Mohammad Reza Zali 6 1 Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran 1985717413, Iran; [email protected] (S.B.G.); [email protected] (H.A.A.); [email protected] (M.F.) 2 Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran 1985717413, Iran; [email protected] (A.Y.); [email protected] (M.A.) 3 IBD Center, Division of Gastroenterology, Virginia Tech Carilion School of Medicine, Roanoke, VA 24016, USA 4 Department of Clinical and Experimental Medical Sciences, University of Udine School of Medicine, 33100 Udine, Italy 5 Department of Internal Medicine, Roanoke Memorial Hospital, Carilion Clinic, VA 24014, USA; [email protected] 6 Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran 1985717413, Iran; [email protected] (H.B.); [email protected] (S.S.); [email protected] (M.R.Z.) * Correspondence: [email protected] These authors equally contributed to this study. y Received: 7 August 2020; Accepted: 27 August 2020; Published: 29 August 2020 Abstract: In inflammatory bowel diseases (IBD), the therapeutic benefit and mucosal healing from specific probiotics may relate to the modulation of dendritic cells (DCs).
    [Show full text]
  • Soluble CD83 Inhibits T Cell Activation by Binding to the TLR4/MD-2 Complex on CD14+ Monocytes
    Soluble CD83 Inhibits T Cell Activation by Binding to the TLR4/MD-2 Complex on CD14+ Monocytes This information is current as Joe M. Horvatinovich, Elizabeth W. Grogan, Marcus Norris, of September 29, 2021. Alexander Steinkasserer, Henrique Lemos, Andrew L. Mellor, Irina Y. Tcherepanova, Charles A. Nicolette and Mark A. DeBenedette J Immunol 2017; 198:2286-2301; Prepublished online 13 February 2017; Downloaded from doi: 10.4049/jimmunol.1600802 http://www.jimmunol.org/content/198/6/2286 Supplementary http://www.jimmunol.org/content/suppl/2017/02/11/jimmunol.160080 http://www.jimmunol.org/ Material 2.DCSupplemental References This article cites 80 articles, 29 of which you can access for free at: http://www.jimmunol.org/content/198/6/2286.full#ref-list-1 Why The JI? Submit online. by guest on September 29, 2021 • Rapid Reviews! 30 days* from submission to initial decision • No Triage! Every submission reviewed by practicing scientists • Fast Publication! 4 weeks from acceptance to publication *average Subscription Information about subscribing to The Journal of Immunology is online at: http://jimmunol.org/subscription Permissions Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html Author Choice Freely available online through The Journal of Immunology Author Choice option Email Alerts Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts The Journal of Immunology is published twice each month by The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2017 by The American Association of Immunologists, Inc. All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606.
    [Show full text]
  • Galectin-4 Interaction with CD14 Triggers the Differentiation of Monocytes Into Macrophage-Like Cells Via the MAPK Signaling Pathway
    Immune Netw. 2019 Jun;19(3):e17 https://doi.org/10.4110/in.2019.19.e17 pISSN 1598-2629·eISSN 2092-6685 Original Article Galectin-4 Interaction with CD14 Triggers the Differentiation of Monocytes into Macrophage-like Cells via the MAPK Signaling Pathway So-Hee Hong 1,2,3,4,5, Jun-Seop Shin 1,2,3,5, Hyunwoo Chung 1,2,4,5, Chung-Gyu Park 1,2,3,4,5,* 1Xenotransplantation Research Center, Seoul National University College of Medicine, Seoul 03080, Korea 2Institute of Endemic Diseases, Seoul National University College of Medicine, Seoul 03080, Korea 3Cancer Research Institute, Seoul National University College of Medicine, Seoul 03080, Korea 4Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul 03080, Korea 5Department of Microbiology and Immunology, Seoul National University College of Medicine, Seoul 03080, Korea Received: Jan 28, 2019 ABSTRACT Revised: May 13, 2019 Accepted: May 19, 2019 Galectin-4 (Gal-4) is a β-galactoside-binding protein mostly expressed in the gastrointestinal *Correspondence to tract of animals. Although intensive functional studies have been done for other galectin Chung-Gyu Park isoforms, the immunoregulatory function of Gal-4 still remains ambiguous. Here, we Department of Microbiology and Immunology, Seoul National University College of Medicine, demonstrated that Gal-4 could bind to CD14 on monocytes and induce their differentiation 103 Daehak-ro, Jongno-gu, Seoul 03080, into macrophage-like cells through the MAPK signaling pathway. Gal-4 induced the phenotypic Korea. changes on monocytes by altering the expression of various surface molecules, and induced E-mail: [email protected] functional changes such as increased cytokine production and matrix metalloproteinase expression and reduced phagocytic capacity.
    [Show full text]
  • B Cell Checkpoints in Autoimmune Rheumatic Diseases
    REVIEWS B cell checkpoints in autoimmune rheumatic diseases Samuel J. S. Rubin1,2,3, Michelle S. Bloom1,2,3 and William H. Robinson1,2,3* Abstract | B cells have important functions in the pathogenesis of autoimmune diseases, including autoimmune rheumatic diseases. In addition to producing autoantibodies, B cells contribute to autoimmunity by serving as professional antigen- presenting cells (APCs), producing cytokines, and through additional mechanisms. B cell activation and effector functions are regulated by immune checkpoints, including both activating and inhibitory checkpoint receptors that contribute to the regulation of B cell tolerance, activation, antigen presentation, T cell help, class switching, antibody production and cytokine production. The various activating checkpoint receptors include B cell activating receptors that engage with cognate receptors on T cells or other cells, as well as Toll-like receptors that can provide dual stimulation to B cells via co- engagement with the B cell receptor. Furthermore, various inhibitory checkpoint receptors, including B cell inhibitory receptors, have important functions in regulating B cell development, activation and effector functions. Therapeutically targeting B cell checkpoints represents a promising strategy for the treatment of a variety of autoimmune rheumatic diseases. Antibody- dependent B cells are multifunctional lymphocytes that contribute that serve as precursors to and thereby give rise to acti- cell- mediated cytotoxicity to the pathogenesis of autoimmune diseases
    [Show full text]
  • The Immunological Synapse and CD28-CD80 Interactions Shannon K
    © 2001 Nature Publishing Group http://immunol.nature.com ARTICLES The immunological synapse and CD28-CD80 interactions Shannon K. Bromley1,Andrea Iaboni2, Simon J. Davis2,Adrian Whitty3, Jonathan M. Green4, Andrey S. Shaw1,ArthurWeiss5 and Michael L. Dustin5,6 Published online: 19 November 2001, DOI: 10.1038/ni737 According to the two-signal model of T cell activation, costimulatory molecules augment T cell receptor (TCR) signaling, whereas adhesion molecules enhance TCR–MHC-peptide recognition.The structure and binding properties of CD28 imply that it may perform both functions, blurring the distinction between adhesion and costimulatory molecules. Our results show that CD28 on naïve T cells does not support adhesion and has little or no capacity for directly enhancing TCR–MHC- peptide interactions. Instead of being dependent on costimulatory signaling, we propose that a key function of the immunological synapse is to generate a cellular microenvironment that favors the interactions of potent secondary signaling molecules, such as CD28. The T cell receptor (TCR) interaction with complexes of peptide and as CD2 and CD48, which suggests that CD28 might have a dual role as major histocompatibility complex (pMHC) is central to the T cell an adhesion and a signaling molecule4. Coengagement of CD28 with response. However, efficient T cell activation also requires the partici- the TCR has a number of effects on T cell activation; these include pation of additional cell-surface receptors that engage nonpolymorphic increasing sensitivity to TCR stimulation and increasing the survival of ligands on antigen-presenting cells (APCs). Some of these molecules T cells after stimulation5. CD80-transfected APCs have been used to are involved in the “physical embrace” between T cells and APCs and assess the temporal relationship of TCR and CD28 signaling, as initiat- are characterized as adhesion molecules.
    [Show full text]
  • Induces Antigen Presentation in B Cells Cell-Activating Factor of The
    B Cell Maturation Antigen, the Receptor for a Proliferation-Inducing Ligand and B Cell-Activating Factor of the TNF Family, Induces Antigen Presentation in B Cells This information is current as of September 27, 2021. Min Yang, Hidenori Hase, Diana Legarda-Addison, Leena Varughese, Brian Seed and Adrian T. Ting J Immunol 2005; 175:2814-2824; ; doi: 10.4049/jimmunol.175.5.2814 http://www.jimmunol.org/content/175/5/2814 Downloaded from References This article cites 54 articles, 36 of which you can access for free at: http://www.jimmunol.org/content/175/5/2814.full#ref-list-1 http://www.jimmunol.org/ Why The JI? Submit online. • Rapid Reviews! 30 days* from submission to initial decision • No Triage! Every submission reviewed by practicing scientists • Fast Publication! 4 weeks from acceptance to publication by guest on September 27, 2021 *average Subscription Information about subscribing to The Journal of Immunology is online at: http://jimmunol.org/subscription Permissions Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html Email Alerts Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts The Journal of Immunology is published twice each month by The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2005 by The American Association of Immunologists All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. The Journal of Immunology B Cell Maturation Antigen, the Receptor for a Proliferation-Inducing Ligand and B Cell-Activating Factor of the TNF Family, Induces Antigen Presentation in B Cells1 Min Yang,* Hidenori Hase,* Diana Legarda-Addison,* Leena Varughese,* Brian Seed,† and Adrian T.
    [Show full text]
  • Induce EBV-Transformed B Cell Apoptosis Through the Fas/Fasl Pathway
    INTERNATIONAL JOURNAL OF ONCOLOGY 43: 1531-1540, 2013 CD80 (B7.1) and CD86 (B7.2) induce EBV-transformed B cell apoptosis through the Fas/FasL pathway GA BIN PARK1, YEONG SEOK KIM1, HYUN-KYUNG LEE2, DAE-HO CHO3, DAEJIN KIM1 and DAE YOUNG HUR1 1Department of Anatomy and Research Center for Tumor Immunology, Inje University College of Medicine; 2Department of Internal Medicine, Inje University Busan Paik Hospital, Busan 614-735; 3Department of Life Science, Sookmyung Women's University, Yongsan-gu, Yongsan-ku, Seoul 140-742, Republic of Korea Received July 7, 2013; Accepted August 16, 2013 DOI: 10.3892/ijo.2013.2091 Abstract. CD80 and CD86 expression is strongly regulated resting human B lymphocytes with EBV results in immor- in B cells and is induced by various stimuli (e.g., cytokines, talization of infected B cells, yielding lymphoblastoid cells, ligation of MHC class II and CD40 ligand). Epstein-Barr virus which are characterized by continuous growth and resistance (EBV) infection activates B lymphocytes and transforms them to various apoptotic signals. Moreover, lymphoblastoid cells into lymphoblastoid cells. However, the role of CD80 and CD86 have a phenotype related to that of activated B-lymphoblasts. in EBV infection of B cells remains unclear. Here, we observed However, despite clarification of the role of some viral proteins, that cross-linking of CD80 and CD86 in EBV-transformed such as latent membrane protein (LMP), in EBV-related resis- B cells induced apoptosis through caspase-dependent release tance, the molecular mechanisms of resistance to apoptosis are of apoptosis-related molecules, cytochrome c and apoptosis- not yet fully understood (2,3).
    [Show full text]
  • Loss of the Death Receptor CD95 (Fas) Expression by Dendritic Cells Protects from a Chronic Viral Infection
    Loss of the death receptor CD95 (Fas) expression by dendritic cells protects from a chronic viral infection Vineeth Varanasia, Aly Azeem Khanb, and Alexander V. Chervonskya,1 aDepartment of Pathology and Committee on Immunology, and bInstitute for Genomics and Systems Biology and Department of Human Genetics, The University of Chicago, Chicago, IL 60637 Edited* by Alexander Y. Rudensky, Memorial Sloan–Kettering Cancer Center, New York, NY, and approved May 5, 2014 (received for review January 28, 2014) Chronic viral infections incapacitate adaptive immune responses persistsinparenchymatousorganssuchaskidneys(13,15).In by “exhausting” virus-specific T cells, inducing their deletion and contrast, infection with the Armstrong variant of LCMV is rapidly reducing productive T-cell memory. Viral infection rapidly induces cleared, does not cause exhaustion of T cells, and results in the death receptor CD95 (Fas) expression by dendritic cells (DCs), mak- formation of a good memory T-cell response. Animals carrying ing them susceptible to elimination by the immune response. Lym- loxP-flanked Fas exon IX (B6.FasKI) and CD11c-driven Cre phocytic choriomeningitis virus (LCMV) clone 13, which normally recombinase (B6.CD11c-Cre) were infected with LCMV clone 13. establishes a chronic infection, is rapidly cleared in C57Black6/J Cre-negative FasKI mice as well as mice with a T-cell–specific mice with conditional deletion of Fas in DCs. The immune response deletion of Fas (B6.Lck-Cre.FasKI) served as controls (Fig. 1). to LCMV is characterized by an extended survival of virus-specific Viral titers were determined in the secondary lymphoid organs effector T cells. Moreover, transfer of Fas-negative DCs from non- and kidneys.
    [Show full text]
  • Cx3cr1 Mediates the Development of Monocyte-Derived Dendritic Cells During Hepatic Inflammation
    CX3CR1 MEDIATES THE DEVELOPMENT OF MONOCYTE-DERIVED DENDRITIC CELLS DURING HEPATIC INFLAMMATION. Supplementary material Supplementary Figure 1: Liver CD45+ myeloid cells were pre-gated for Ly6G negative cells for excluding granulocytes and HDCs subsequently analyzed among the cells that were CD11c+ and had high expression of MHCII. Supplementary Table 1 low/- high + Changes in gene expression between CX3CR1 and CX3CR1 CD11b myeloid hepatic dendritic cells (HDCs) from CCl4-treated mice high Genes up-regulated in CX3CR1 HDCs Gene Fold changes P value Full name App 4,01702 5,89E-05 amyloid beta (A4) precursor protein C1qa 9,75881 1,69E-22 complement component 1, q subcomponent, alpha polypeptide C1qb 9,19882 3,62E-20 complement component 1, q subcomponent, beta polypeptide Ccl12 2,51899 0,011769 chemokine (C-C motif) ligand 12 Ccl2 6,53486 6,37E-11 chemokine (C-C motif) ligand 2 Ccl3 4,99649 5,84E-07 chemokine (C-C motif) ligand 3 Ccl4 4,42552 9,62E-06 chemokine (C-C motif) ligand 4 Ccl6 3,9311 8,46E-05 chemokine (C-C motif) ligand 6 Ccl7 2,60184 0,009272 chemokine (C-C motif) ligand 7 Ccl9 4,17294 3,01E-05 chemokine (C-C motif) ligand 9 Ccr2 3,35195 0,000802 chemokine (C-C motif) receptor 2 Ccr5 3,23358 0,001222 chemokine (C-C motif) receptor 5 Cd14 6,13325 8,61E-10 CD14 antigen Cd36 2,94367 0,003243 CD36 antigen Cd44 4,89958 9,60E-07 CD44 antigen Cd81 6,49623 8,24E-11 CD81 antigen Cd9 3,06253 0,002195 CD9 antigen Cdkn1a 4,65279 3,27E-06 cyclin-dependent kinase inhibitor 1A (P21) Cebpb 6,6083 3,89E-11 CCAAT/enhancer binding protein (C/EBP),
    [Show full text]
  • (Siglec) Adhesion Receptor That Binds CD83
    CD83 Is a Sialic Acid-Binding Ig-Like Lectin (Siglec) Adhesion Receptor that Binds Monocytes and a Subset of Activated CD8+ T Cells This information is current as of September 25, 2021. Nathalie Scholler, Martha Hayden-Ledbetter, Karl-Erik Hellström, Ingegerd Hellström and Jeffrey A. Ledbetter J Immunol 2001; 166:3865-3872; ; doi: 10.4049/jimmunol.166.6.3865 http://www.jimmunol.org/content/166/6/3865 Downloaded from References This article cites 44 articles, 21 of which you can access for free at: http://www.jimmunol.org/content/166/6/3865.full#ref-list-1 http://www.jimmunol.org/ Why The JI? Submit online. • Rapid Reviews! 30 days* from submission to initial decision • No Triage! Every submission reviewed by practicing scientists • Fast Publication! 4 weeks from acceptance to publication by guest on September 25, 2021 *average Subscription Information about subscribing to The Journal of Immunology is online at: http://jimmunol.org/subscription Permissions Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html Email Alerts Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts Errata An erratum has been published regarding this article. Please see next page or: /content/182/3/1772.2.full.pdf The Journal of Immunology is published twice each month by The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2001 by The American Association of Immunologists All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. CD83 Is a Sialic Acid-Binding Ig-Like Lectin (Siglec) Adhesion Receptor that Binds Monocytes and a Subset of Activated CD8؉ T Cells1 Nathalie Scholler,2* Martha Hayden-Ledbetter,† Karl-Erik Hellstro¨m,* Ingegerd Hellstro¨m,* and Jeffrey A.
    [Show full text]
  • Anti-Human CD80/B7.1
    Product Information Sheet Anti-Human CD80 (B7-1)-162Dy Catalog #: 3162010B Clone: 2D10.4 Package Size: 100 tests Isotype: Mouse IgG1 Storage: Store product at 4°C. Do not freeze. Formulation: Antibody stabilizer with 0.05% Sodium Azide Cross Reactivity: Rhesus Technical Information Validation: Each lot of conjugated antibody is quality control tested by CyTOF® analysis of stained cells using the appropriate positive and negative cell staining and/or activation controls. Recommended Usage: The suggested use is 1 µl for up to 3 X 106 live cells in 100 µl. It is recommended that the antibody be titrated for optimal performance for each of the desired applications. Human Daudi cells (top) and human Jurkat T cells (bottom) stained with 162Dy- anti-CD80 [B7.1] (2D10.4). Description CD80 (B7.1) is a 60 kDa member of the B7 family of proteins. CD80 is expressed by activated B and T lymphocytes, macrophages and dendritic cells. While CD80 can bind to the immune-stimulatory CD28, it binds with higher affinity to the immune-inhibitory CTLA-4. The B7 ligands CD80 and CD86 and their receptors CD28 and CTLA-4 act create a costimulatory-coinhibitory system that acts to regulate immune responses. Mice deficient in CD80 and CD86 have profound defects in both humoral and cellular immunity. References Bandura, D. R., et al. Mass Cytometry: Technique for Real Time Single Cell Multitarget Immunoassay Based on Inductively Coupled Plasma Time-of-Flight Mass Spectrometry. Analytical Chemistry 81:6813-6822, 2009. Ornatsky, O. I., et al. Highly multiparametric analysis by mass cytometry. J Immunol Methods 361 (1-2):1-20, 2010.
    [Show full text]