DOCSLIB.ORG

A New Vampire Saga: the Molecular Mechanism of T Cell Trogocytosis

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
A New Vampire Saga: the Molecular Mechanism of T Cell Trogocytosis View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Elsevier - Publisher Connector Immunity Previews protect against severe disease. This is type I IFNs in malaria infection. The pres- Herbich, K., Schmid, D., et al. (2000). Infect. Immun. consistent with the finding that recombi- ence of AT-rich motifs in the genomes of 68, 3909–3915. nant IFN-a administration early in PbA other protozoa, bacteria, and humans Parroche, P., Lauw, F.N., Goutagny, N., Latz, E., infection reduced parasitemia and pro- suggests that these motifs could con- Monks, B.G., Visintin, A., Halmen, K.A., Lamphier, M., Olivier, M., Bartholomeu, D.C., et al. (2007). tected against ECM in a IFN-g-dependent tribute to the pathogenesis of other Proc. Natl. Acad. Sci. USA 104, 1919–1924. manner (Vigario et al., 2007). A beneficial severe infectious syndromes. In the case effect of type I IFNs was also suggested of extracellular DNA sources, it is in- Sharma, S., DeOliveira, R.B., Kalantari, P., Parroche, P., Goutagny, N., Jiang, Z., Chan, J., by higher plasma IFN-a levels in African triguing to consider that other crystals Bartholomeu, D.C., Lauw, F., Hall, J.P., et al. children with mild malaria compared to (e.g., urate) may move these motifs into (2011). Immunity 35, this issue, 194–207. those with hyperparasitemia or severe the cytosol for innate sensing. This pro- Shimosato, T., Kimura, T., Tohno, M., Iliev, I.D., malarial anemia (Luty et al., 2000). The posed mechanism, if confirmed, may Katoh, S., Ito, Y., Kawai, Y., Sasaki, T., Saito, T., heterogeneity and complexity of human have relevance for the development of and Kitazawa, H. (2006). Cell. Microbiol. 8, severe malaria necessitate examining DNA-based vaccine adjuvants. 485–495. the role of type I IFNs in diverse patient Shio, M.T., Eisenbarth, S.C., Savaria, M., Vinet, populations and in multiple murine A.F., Bellemare, M.J., Harder, K.W., Sutterwala, REFERENCES F.S., Bohle, D.S., Descoteaux, A., Flavell, R.A., models representing different aspects of and Olivier, M. (2009). PLoS Pathog. 5, e1000559. human disease. However, the present findings do caution against administration Coban, C., Ishii, K.J., Kawai, T., Hemmi, H., Sato, van der Heyde, H.C., Nolan, J., Combes, V., S., Uematsu, S., Yamamoto, M., Takeuchi, O., Gramaglia, I., and Grau, G.E. (2006). Trends of type I IFNs as adjunctive therapy for Itagaki, S., Kumar, N., et al. (2005). J. Exp. Med. Parasitol. 22, 503–508. CM, especially because patients typically 201, 19–25. present with advanced pathology. Vigario, A.M., Belnoue, E., Gruner, A.C., Mauduit, Lovegrove, F.E., Gharib, S.A., Patel, S.N., Hawkes, M., Kayibanda, M., Deschemin, J.C., Marussig, In summary, Sharma et al. (2011) C.A., Kain, K.C., and Liles, W.C. (2007). Am. J. M., Snounou, G., Mazier, D., Gresser, I., and Renia, identify a unique cytosolic DNA sensing Pathol. 171, 1894–1903. L. (2007). J. Immunol. 178, 6416–6425. pathway and considerably expand our Luty, A.J., Perkins, D.J., Lell, B., Schmidt-Ott, R., Wu, X., Gowda, N.M., Kumar, S., and Gowda, D.C. knowledge of the induction and role of Lehman, L.G., Luckner, D., Greve, B., Matousek, P., (2010). J. Immunol. 184, 4338–4348. A New Vampire Saga: The Molecular Mechanism of T Cell Trogocytosis Elaine Pashupati Dopfer,1 Susana Minguet,1 and Wolfgang W.A. Schamel1,* 1Department of Molecular Immunology, Faculty of Biology, BIOSS Centre for Biological Signalling Studies, Center for Chronic Immunodeficiency (CCI) and Max-Planck-Institute for Immunbiology and Epigenetics, Stu¨ beweg 51, 79108 Freiburg, Germany *Correspondence: [email protected] DOI 10.1016/j.immuni.2011.08.004 In the current issue of Immunity, Martı´nez-Martı´n et al. (2011) describe the central supramolecular activation cluster (cSMAC) as a site of clathrin-independent T cell receptor (TCR) internalization and trogocytosis. Further, they identify small Rho GTPases TC21 and RhoG as key mediators of these processes. Cell-to-cell communication is essential for senting cell (APC) to a lymphocyte (Joly in vitro and in vivo. Trogocytosis can be the orchestration of the immune system and Hudrisier, 2003). This is in strong distinguished from other mechanisms of and its responses. Although immune cells contrast to phagocytosis, the process of intercellular transfer because it requires normally communicate through either engulfing whole pathogens and death close cell-cell contact, is quick (within soluble or membrane-bound mediators, cell fragments by phagocytes. minutes), and involves transfer of intact new types of cellular interchange have The first evidence of trogocytosis was proteins. Previous studies focused on the been described, including trogocytosis, the transfer of major histocompatibility celltypes involvedand the molecules trans- exosome secretion, and nanotube forma- complex class II (MHCII) glycoproteins ferred, but the molecular mechanism that tion. The term trogocytosis (from Greek from B to T cells (Cone et al., 1972). Since underpins this phenomenon has remained trogo-, nibble) was originally coined to then, trogocytotic activity has been re- largely unknown. Trogocytosis is an active describe the intercellular transfer of ported for T, B, natural killer (NK), and process in T and NK cells, requiring both membrane patches from an antigen-pre- dendritic cells and is well documented receptor signaling and actin cytoskeleton Immunity 35, August 26, 2011 ª2011 Elsevier Inc. 151 Immunity Previews MHCp APC cellular vesicles, and shRNA-mediated TCR silencing of clathrin did not affect TCR nanocluster and TC21 cointernalization. The authors Re-expression TCR also have shown by electron microscopy T cell microcluster that, in contrast to the pSMAC, the cSMAC is devoid of clathrin-coated pits. Clathrin Altogether, the authors propose a model Signal in which triggered TCRs are internalized TC21 PI3K Trogocytosis at the cSMAC by a TC21-dependent RhoG but clathrin-independent mechanism. In Actin contrast, homeostatic clathrin-mediated internalization might take place in the Degradation pSMAC cSMAC Signal Degradation pSMAC. Additionally, RhoG was identified as a Figure 1. TCR Internalization and Trogocytosis in T Cells player in TC21-dependent TCR internali- Constitutive TCR turnover occurs in resting cells. Upon stimulation, TCR nanoclusters aggregate to zation. Like TC21, RhoG must cycle be- signaling-active microclusters that can be internalized in the pSMAC in a clathrin-dependent manner. tween active and inactive conformations Once the microclusters have reached the cSMAC, patches of the APC containing the pMHC molecules are trogocytosed with a TC21- and RhoG-dependent mechanism. Trogocytosed membrane proteins to promote TCR internalization from the from the APC can be re-expressed on the T cell. cSMAC. Because RhoG was first de- scribed in the phagocytosis of apoptotic bodies (Henson, 2005), the authors inves- remodeling. In this issue of Immunity,the was added when analyzing ligands of tigated the capability of T cells to phago- group of Balbino Alarco´ nprovidesnew different qualities, given that the cSMAC cytose anti-TCR-coupled latex beads. It insights into the molecular mechanism can enhance stimulation by weak agonists was surprising that primary T cells were that drives T cell antigen receptor (TCR)- (Cemerski et al., 2008). TCR stimulation by able to phagocytose beads that were as mediated trogocytosis by identifying the pMHC leads to TCR downmodulation, big as themselves, which they accommo- small GTPases TC21 and RhoG as key mainly by increasing TCR degradation, dated through massive reorganization of players (Martı´nez-Martı´n et al., 2011). because clathrin-mediated TCR endocy- their cytoplasm and plasma membrane. On resting T cells, the TCR coexists in tosis is unchanged (Liu et al., 2000). How- TCR-driven phagocytosis of beads was monomeric and nanoclustered forms ever, intense TCR stimulation leads to impaired in T lymphocytes derived from (Schamel et al., 2005). The amount of marginal acceleration of TCR internaliza- TC21- or RhoG-deficient mice when TCR expressed on the cell surface is tion by a second, clathrin-independent compared to wild-type controls. In stimu- tightly controlled by the rates of TCR pathway (Monjas, 2004). Yet, detailed lated T cells from TC21- and RhoG-defi- synthesis, constitutive clathrin-mediated insight into when and where clathrin- cient mice, total downregulation of the TCR internalization, recycling and degra- dependent or -independent internalization TCR was only slightly affected, suggest- dation (Figure 1). Once the T cell is stimu- occurs is still missing. ing that clathrin-mediated internalization lated by antigenic peptides presented on In the present article, Martı´nez-Martı´n was prominent. In contrast, acquisition MHC (pMHC), the TCRs aggregate to et al. identify the cSMAC as the site of of membrane patches and MHC mole- form microclusters. These pMHC-in- clathrin-independent TCR internalization cules by trogocytosis was greatly de- duced microclusters contain phosphory- and report that together with the inter- creased in CD4+ and CD8+ T cells. lated TCRs that initiate activation of the nalized TCR, membrane patches and Further, acquisition of membrane patches cell. Subsequently, the microclusters coa- pMHC complexes from the APC are and TCR-triggered phagocytosis were lesce to form the central supramolecular trogocytosed. actin dependent and probably equivalent activation cluster (cSMAC) surrounded Using time-lapse confocal videomicro- phenomena. by the peripheral SMAC (pSMAC), to- scopy and primary T cells derived from Using pharmacological inhibitors, gether forming an immune synapse. The genetically ablated mice, they have shown Martı´nez-Martı´n et al. showed that inacti- functional significance of the cSMAC has that TCR internalization from the cSMAC vation of phosphatidyl inositol-3 kinase been the subject of recent controversy. is dependent on the small GTPases (PI3K) reduced the phagocytosis of beads Originally, it had been proposed that accu- TC21 and RhoG. TC21 is constitutively as well as membrane acquisition by mulation of engaged receptors and sig- associated with the TCR and co-translo- trogocytosis.
Load more

Recommended publications
  • Trogocytosis of Peptide–MHC Class II Complexes from Dendritic Cells Confers Antigen-Presenting Ability on Basophils
    Trogocytosis of peptide–MHC class II complexes from dendritic cells confers antigen-presenting ability on basophils Kensuke Miyakea, Nozomu Shiozawaa, Toshihisa Nagaoa, Soichiro Yoshikawaa, Yoshinori Yamanishia, and Hajime Karasuyamaa,1 aDepartment of Immune Regulation, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Tokyo 113-8510, Japan Edited by Ruslan Medzhitov, Yale University School of Medicine, New Haven, CT, and approved December 7, 2016 (received for review September 26, 2016) Th2 immunity plays important roles in both protective and allergic function as antigen-presenting cells (APCs) and induce Th2 dif- responses. Nevertheless, the nature of antigen-presenting cells ferentiation in cooperation with basophil-derived IL-4. responsible for Th2 cell differentiation remains ill-defined com- Reports from three independent groups further expanded the pared with the nature of the cells responsible for Th1 and Th17 cell role for basophils in Th2 differentiation and demonstrated in differentiation. Basophils have attracted attention as a producer of three distinct experimental settings that basophils, rather than Th2-inducing cytokine IL-4, whereas their MHC class II (MHC-II) DCs, are the critical APCs for driving Th2 differentiation (5–7). expression and function as antigen-presenting cells are matters of In all settings, basophils expressed both MHC class II (MHC-II) considerable controversy. Here we revisited the MHC-II expression and costimulatory molecules (CD80, CD86, or CD40) necessary for on basophils and explored its functional relevance in Th2 cell APC function, and could process and present antigens. Depletion differentiation. Basophils generated in vitro from bone marrow of basophils but not DCs abolished Th2 differentiation in vivo.
    [Show full text]
  • PD-L1 and B7-1 Cis-Interaction: New Mechanisms in Immune Checkpoints and Immunotherapies
    Trends in Molecular Medicine Opinion PD-L1 and B7-1 Cis-Interaction: New Mechanisms in Immune Checkpoints and Immunotherapies Christopher D. Nishimura,1,6 Marc C. Pulanco,1,6 Wei Cui,2 Liming Lu,3 and Xingxing Zang1,4,5,* Immune checkpoints negatively regulate immune cell responses. Programmed Highlights cell death protein 1:programmed death ligand 1 (PD-1:PD-L1) and cytotoxic Dysregulation of immune checkpoints T lymphocyte-associated protein 4 (CTLA-4):B7-1 are among the most important contributes to the pathogenesis of immune checkpoint pathways, and are key targets for immunotherapies that cancer, autoimmunity, and organ trans- plant rejection by mediating undesired seek to modulate the balance between stimulatory and inhibitory signals to lead immune responses. to favorable therapeutic outcomes. The current dogma of these two immune checkpoint pathways has regarded them as independent with no interactions. The limited long-term therapeutic effi- However, the newly characterized PD-L1:B7-1 ligand–ligand cis-interaction and cacy of immunotherapies targeting immune checkpoints underscores the its ability to bind CTLA-4 and CD28, but not PD-1, suggests that these pathways need to better understand the underlying have significant crosstalk. Here, we propose that the PD-L1:B7-1 cis-interaction biology of these proteins. brings novel mechanistic understanding of these pathways, new insights into – mechanisms of current immunotherapies, and fresh ideas to develop better Immune checkpoint receptor ligand interactions most commonly occur in treatments in a variety of therapeutic settings. trans (e.g., the receptor and ligand are expressed on two different cells). The newly characterized PD-L1:B7-1 interac- tion occurs in cis (e.g., the receptor and Immune Checkpoint Blockade ligandareexpressedonthesamecell).
    [Show full text]
  • Investigating the Role of CR3 in Trogocytosis of Trichomonas Vaginalis Cells by Neutrophil-Like Cells
    Investigating the role of CR3 in trogocytosis of Trichomonas vaginalis cells by Neutrophil-like cells. Senior Thesis California State Polytechnic University, Department of Biology Aljona Leka Team Members: Jose Moran Mercer Lab Spring 2020 Table of Contents 1. Abstract 2. Introduction 3. Results a) PLB-985 cells differentiate into Neutrophil-like cells b) Strategy for functional deletion of CD11b c) Generation of CD11b knockout cell lines with CRISPR-Cas9 gene editing system showed low cell viability post transfection d) NLCs kill T. vaginalis in the presence of human serum e) NLCs kill T. vaginalis in the presence of heat inactivated human serum 4. Methods a. Promyelocytic cell lines and culture b. Immunolabeling for CD11b and CD18 c. Generation of genetically modified cells d. Culturing transfectants e. Single cell dilution f. Culturing T. vaginalis cells g. Cytotoxicity assay h. Plasmid Construction i. Isolating the px459construct for transfection 5. Discussion 6. References 7. Acknowledgements 8. Supporting information Abstract Trichomonas vaginalis (T. vaginalis) causes the non-viral sexually transmitted infection (STI), trichomoniasis. Trichomoniasis affected almost 276.4 million people globally in 2008 alone, with most incidents occurring in underserved communities. The main curative treatment for T. vaginalis is an antibiotic, Metronidazole, though antibiotic resistance is on the rise. Neutrophils are the first responders against T. vaginalis, killing the parasite through a recently discovered process called trogocytosis, in which the neutrophils “nibble” on the parasite’s membrane leading to killing of the parasite. However, current literature lacks the knowledge of which molecular components are involved in trogocytosis of T. vaginalis. Trogocytosis is a contact- dependent process mediated through opsonins, specifically iC3b, which serves as a tag to make the pathogens “tasty” for the neutrophils.
    [Show full text]
  • T Cells Via Trogocytosis + Apcs Onto CD8 Programmed Death Ligand 1
    Antigen-Specific Transfer of Functional Programmed Death Ligand 1 from Human APCs onto CD8+ T Cells via Trogocytosis This information is current as Regina Gary, Simon Voelkl, Ralf Palmisano, Evelyn Ullrich, of October 1, 2021. Jacobus J. Bosch and Andreas Mackensen J Immunol 2012; 188:744-752; Prepublished online 14 December 2011; doi: 10.4049/jimmunol.1101412 http://www.jimmunol.org/content/188/2/744 Downloaded from Supplementary http://www.jimmunol.org/content/suppl/2011/12/14/jimmunol.110141 Material 2.DC1 http://www.jimmunol.org/ References This article cites 44 articles, 23 of which you can access for free at: http://www.jimmunol.org/content/188/2/744.full#ref-list-1 Why The JI? Submit online. • Rapid Reviews! 30 days* from submission to initial decision • No Triage! Every submission reviewed by practicing scientists by guest on October 1, 2021 • 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 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 © 2012 by The American Association of Immunologists, Inc. All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. The Journal of Immunology Antigen-Specific Transfer of Functional Programmed Death Ligand 1 from Human APCs onto CD8+ T Cells via Trogocytosis Regina Gary,* Simon Voelkl,* Ralf Palmisano,† Evelyn Ullrich,* Jacobus J.
    [Show full text]
  • Trogocytosis of Peptide–MHC Class II Complexes from Dendritic Cells Confers Antigen-Presenting Ability on Basophils
    Trogocytosis of peptide–MHC class II complexes from dendritic cells confers antigen-presenting ability on basophils Kensuke Miyakea, Nozomu Shiozawaa, Toshihisa Nagaoa, Soichiro Yoshikawaa, Yoshinori Yamanishia, and Hajime Karasuyamaa,1 aDepartment of Immune Regulation, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Tokyo 113-8510, Japan Edited by Ruslan Medzhitov, Yale University School of Medicine, New Haven, CT, and approved December 7, 2016 (received for review September 26, 2016) Th2 immunity plays important roles in both protective and allergic function as antigen-presenting cells (APCs) and induce Th2 dif- responses. Nevertheless, the nature of antigen-presenting cells ferentiation in cooperation with basophil-derived IL-4. responsible for Th2 cell differentiation remains ill-defined com- Reports from three independent groups further expanded the pared with the nature of the cells responsible for Th1 and Th17 cell role for basophils in Th2 differentiation and demonstrated in differentiation. Basophils have attracted attention as a producer of three distinct experimental settings that basophils, rather than Th2-inducing cytokine IL-4, whereas their MHC class II (MHC-II) DCs, are the critical APCs for driving Th2 differentiation (5–7). expression and function as antigen-presenting cells are matters of In all settings, basophils expressed both MHC class II (MHC-II) considerable controversy. Here we revisited the MHC-II expression and costimulatory molecules (CD80, CD86, or CD40) necessary for on basophils and explored its functional relevance in Th2 cell APC function, and could process and present antigens. Depletion differentiation. Basophils generated in vitro from bone marrow of basophils but not DCs abolished Th2 differentiation in vivo.
    [Show full text]
  • Macrophage-Mediated Trogocytosis Leads to Death of Antibody-Opsonized Tumor Cells Ramraj Velmurugan1,2,3,5, Dilip K
    Published OnlineFirst May 25, 2016; DOI: 10.1158/1535-7163.MCT-15-0335 Large Molecule Therapeutics Molecular Cancer Therapeutics Macrophage-Mediated Trogocytosis Leads to Death of Antibody-Opsonized Tumor Cells Ramraj Velmurugan1,2,3,5, Dilip K. Challa1,2,3,5, Sripad Ram5, Raimund J. Ober1,4,5,and E. Sally Ward1,2,5 Abstract Understanding the complex behavior of effector cells such as we demonstrate that persistent trogocytic attack results in the monocytes or macrophages in regulating cancerous growth is of killing of HER2-overexpressing breast cancer cells. Further, central importance for cancer immunotherapy. Earlier studies antibody engineering to increase FcgR interactions enhances using CD20-specific antibodies have demonstrated that the Fcg this tumoricidal activity. These studies extend the complex receptor (FcgR)–mediated transfer of the targeted receptors repertoire of activities of macrophages to trogocytic-mediated from tumor cells to these effector cells through trogocytosis cell death of HER2-overexpressing target cells and have impli- canenableescapefromantibody therapy, leading to the view- cations for the development of effective antibody-based ther- point that this process is protumorigenic. In the current study, apies. Mol Cancer Ther; 15(8); 1–11. Ó2016 AACR. Introduction of escape has been extensively studied for anti-CD20 antibodies (2, 3, 8, 9) and involves the depletion of target antigen from the Defining the consequences of the interactions of immune cell surface combined with the exhaustion of effector pathways. effector cells with cancer cells in the presence of tumor-specific These observations have led to the development of dosing regi- antibodies has direct relevance to both immunosurveillance and mens to reduce trogocytosis and minimize the protumorigenic cancer therapy.
    [Show full text]
  • What Is Trogocytosis and What Is Its Purpose?
    CORRESPONDENCE What is trogocytosis and what is its purpose? To the editor: lymphocytes, may directly or indirectly pathogens. Because of their mobility, Several reports have documented that influence the phenotype and function of lymphocytes could contribute to the spread lymphocytes can extract surface molecules the lymphocytes. From an evolutionary of pathogens within the host either through through the ‘immunological synapse’ from perspective, trogocytosis may have developed direct capture of the pathogen or its the antigen-presenting cells to which they are initially as a symbiotic arrangement: genome6 (for example, prions or human conjugated1. This phenomenon, which we leukocytes may be ‘feeding’ off other cell immunodeficiency virus) or of cell surface have called ‘trogocytosis’1 (from the ancient types in return for undertaking the defense viral receptors from other cells7. Greek trogo, meaning ‘gnaw’), involves the of the organism against pathogens. Because We believe trogocytosis may have first transfer of plasma membrane fragments lipids are the most energetically demanding appeared in very primitive organisms as from the presenting cell to the lymphocyte. components to generate, fragments of a way for specialized cell types to feed off http://www.nature.com/natureimmunology Trogocytosis has been documented in T, B plasma membrane acquired by lymphocytes other cells. Subsequently, direct transfer of and natural killer cells both in vitro and in could contribute substantially to their regulatory molecules may have contributed vivo. Thus, this process may be important in metabolic balance, thereby increasing their to the establishment of intercellular the induction and regulation of immune capacity to proliferate. communications. Of course, lymphocyte responses, and possibly in the control of Trogocytosis could be a vector for activation through trogocytosis would have other cellular systems1.
    [Show full text]
  • Monocytes and Granulocytes Reduce CD38 Expression Levels on Myeloma Cells in Patients Treated with Daratumumab Jakub Krejcik1,2, Kris A
    Published OnlineFirst October 12, 2017; DOI: 10.1158/1078-0432.CCR-17-2027 Cancer Therapy: Clinical Clinical Cancer Research Monocytes and Granulocytes Reduce CD38 Expression Levels on Myeloma Cells in Patients Treated with Daratumumab Jakub Krejcik1,2, Kris A. Frerichs1, Inger S. Nijhof1, Berris van Kessel1, Jeroen F. van Velzen3, Andries C. Bloem3, Marloes E.C. Broekmans1, Sonja Zweegman1, Johan van Meerloo1, Rene J.P. Musters4, Pino J. Poddighe5, Richard W.J. Groen1, Christopher Chiu6, Torben Plesner2, Henk M. Lokhorst1, A. Kate Sasser6, Tuna Mutis1, and Niels W.C.J. van de Donk1 Abstract Purpose: Daratumumab treatment results in a marked reduc- during therapy. In-depth analyses revealed that CD38 levels of tion of CD38 expression on multiple myeloma cells. The aim of multiple myeloma cells were only reduced in the presence of this study was to investigate the clinical implications and the complement or effector cells, suggesting that the rapid elimina- underlying mechanisms of daratumumab-mediated CD38 tion of CD38high multiple myeloma cells can contribute to CD38 reduction. reduction. In addition, we discovered that daratumumab–CD38 Experimental Design: We evaluated the effect of daratumu- complexes and accompanying cell membrane were actively trans- mab alone or in combination with lenalidomide-dexameth- ferred from multiple myeloma cells to monocytes and granulo- asone, on CD38 levels of multiple myeloma cells and non- cytes. This process of trogocytosis was also associated with tumor immune cells in the GEN501 study (daratumumab reduced surface levels of some other membrane proteins, includ- monotherapy) and the GEN503 study (daratumumab com- ing CD49d, CD56, and CD138. bined with lenalidomide-dexamethasone).
    [Show full text]
  • Natural Killer Cell Subsets in Hematological Diseases: Learning
    Natural Killer cell subsets in hematological diseases : learning for immunotherapy Dang Nghiem Vo To cite this version: Dang Nghiem Vo. Natural Killer cell subsets in hematological diseases : learning for immunotherapy. Human health and pathology. Université Montpellier, 2018. English. NNT : 2018MONTT013. tel- 01868212 HAL Id: tel-01868212 https://tel.archives-ouvertes.fr/tel-01868212 Submitted on 5 Sep 2018 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. THÈSE POUR OBTENIR LE GRADE DE DOCTEUR DE L’UNIVERSITÉ DE M ONTPELLIER En Biologie Santé École doctorale CBS2 n°168 - Sciences Chimiques et Biologiques pour la Santé Unité de recherche INSERM U1183 - Institut de Médecine Régénératrice et de Biothérapie (IRMB) Natural Killer cell subsets in hematological diseases : learning for immunotherapy Présentée par Dang Nghiem VO Le 03 Juillet 2018 Sous la direction de Dr. Martin VILLALBA-GONZALEZ Devant le jury composé de Prof. Marie-Alix POUL, PU, Institut de Recherche en Cancerologie de Montpellier (IRCM) Président du Jury Dr. Julian PARDO, DR, Biomedical Research Center of Aragon (CIBA), Zaragoza, Espagne Rapporteur Dr. Cyril FAURIAT, CR, Centre de Recherche en Cancérologie de Marseille (CRCM) Rapporteur Dr. Laurent GROS, CR, Institut de Recherche en Cancerologie de Montpellier (IRCM) Examinateur Dr.
    [Show full text]
  • Shaping of T Cell Functions by Trogocytosis
    cells Review Shaping of T Cell Functions by Trogocytosis Masafumi Nakayama *, Arisa Hori, Saori Toyoura and Shin-Ichiro Yamaguchi Laboratory of Immunology and Microbiology, College of Pharmaceutical Sciences, Ritsumeikan University, Shiga 525-8577, Japan; [email protected] (A.H.); [email protected] (S.T.); [email protected] (S.-I.Y.) * Correspondence: [email protected]; Tel.: +81-77-599-3264 Abstract: Trogocytosis is an active process whereby plasma membrane proteins are transferred from one cell to the other cell in a cell-cell contact-dependent manner. Since the discovery of the intercellular transfer of major histocompatibility complex (MHC) molecules in the 1970s, trogocytosis of MHC molecules between various immune cells has been frequently observed. For instance, antigen-presenting cells (APCs) acquire MHC class I (MHCI) from allografts, tumors, and virally infected cells, and these APCs are subsequently able to prime CD8+ T cells without antigen processing via the preformed antigen-MHCI complexes, in a process called cross-dressing. T cells also acquire MHC molecules from APCs or other target cells via the immunological synapse formed at the cell-cell contact area, and this phenomenon impacts T cell activation. Compared with naïve and effector T cells, T regulatory cells have increased trogocytosis activity in order to remove MHC class II and costimulatory molecules from APCs, resulting in the induction of tolerance. Accumulating evidence suggests that trogocytosis shapes T cell functions in cancer, transplantation, and during microbial infections. In this review, we focus on T cell trogocytosis and the related inflammatory diseases. Keywords: acquisition; nibbling; stripping; cross-dressed; cross-presentation; dendritic cell (DC); TCR; Treg; chimeric antigen receptor (CAR); fratricide; escape variant Citation: Nakayama, M.; Hori, A.; Toyoura, S.; Yamaguchi, S.-I.
    [Show full text]
  • Trogocytosis Between Non-Immune Cells for Cell Clearance, and Among Immune-Related Cells for Modulating Immune Responses and Autoimmunity
    International Journal of Molecular Sciences Review Trogocytosis between Non-Immune Cells for Cell Clearance, and among Immune-Related Cells for Modulating Immune Responses and Autoimmunity Ko-Jen Li 1 , Cheng-Han Wu 1,2, Cheng-Hsun Lu 1,2, Chieh-Yu Shen 1,2 , Yu-Min Kuo 1, Chang-Youh Tsai 3 , Song-Chou Hsieh 1,* and Chia-Li Yu 1,* 1 Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei 10002, Taiwan; [email protected] (K.-J.L.); [email protected] (C.-H.W.); [email protected] (C.-H.L.); [email protected] (C.-Y.S.); [email protected] (Y.-M.K.) 2 Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei 10002, Taiwan 3 Division of Allergy, Immunology & Rheumatology, Taipei Veterans General Hospital, Taipei 11210, Taiwan; [email protected] * Correspondence: [email protected] (S.-C.H.); [email protected] (C.-L.Y.); Tel.: +886-2-23123456 (ext. 65909) (S.-C.H.); +886-2-23123456 (ext. 65011) (C.-L.Y.) Abstract: The term trogocytosis refers to a rapid bidirectional and active transfer of surface membrane fragment and associated proteins between cells. The trogocytosis requires cell-cell contact, and exhibits fast kinetics and the limited lifetime of the transferred molecules on the surface of the acceptor cells. The biological actions of trogocytosis include information exchange, cell clearance Citation: Li, K.-J.; Wu, C.-H.; Lu, of unwanted tissues in embryonic development, immunoregulation, cancer surveillance/evasion, C.-H.; Shen, C.-Y.; Kuo, Y.-M.; Tsai, allogeneic cell survival and infectious pathogen killing or intercellular transmission.
    [Show full text]
  • Tasmanian Devil CD28 and CTLA4 Capture CD80 and CD86
    bioRxiv preprint doi: https://doi.org/10.1101/2020.06.11.145789; this version posted June 12, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC 4.0 International license. 1 Title 2 Tasmanian devil CD28 and CTLA4 capture CD80 and CD86 from adjacent cells 3 4 Running title 5 Intercellular protein transfer of immune checkpoints in Tasmanian devils 6 7 Article Type 8 Short Communications 9 10 Authors 11 Candida Wonga, Jocelyn M. Darbya, Peter R. Murphya,b, Terry L. Pinfoldc, Patrick R. 12 Lennardd, Gregory M Woodsa, A. Bruce Lyonsc, Andrew S. Fliesa* 13 14 Affiliations 15 aMenzies Institute for Medical Research, College of Health and Medicine, University of 16 Tasmania, Hobart, TAS 7000, Australia 17 bUniversity of Queensland Diamantina Institute, The University of Queensland, Translational 18 Research Institute, Woolloongabba, Queensland, Australia 19 cTasmanian School of Medicine, College of Health and Medicine, University of Tasmania, 20 Hobart, TAS 7000, Australia 21 dThe Roslin Institute and Royal School of Veterinary Studies, University of Edinburgh, 22 Easter Bush Campus, Midlothian, EH25 9RG, UK. 23 24 Corresponding author 25 Andrew S. Flies, PhD 26 Menzies Institute for Medical Research, College of Health and Medicine 27 University of Tasmania 28 Private Bag 23, Hobart TAS 7000 29 phone: +61 3 6226 4614; email: [email protected] 30 31 32 bioRxiv preprint doi: https://doi.org/10.1101/2020.06.11.145789; this version posted June 12, 2020.
    [Show full text]