A Guide to Human Immune Cell Characterization by Flow Cytometry Immune Cell Characterization by Flow Cytometry
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Natural Killer Cells and Current Applications of Chimeric Antigen Receptor-Modified NK-92 Cells in Tumor Immunotherapy
International Journal of Molecular Sciences Review Natural Killer Cells and Current Applications of Chimeric Antigen Receptor-Modified NK-92 Cells in Tumor Immunotherapy Jianguang Zhang, Huifang Zheng and Yong Diao * School of Medicine, Huaqiao University, Quanzhou 362021, Fujian, China; [email protected] (J.Z.); [email protected] (H.Z.) * Correspondence: [email protected]; Tel.: +86-595-2269-2516 Received: 15 November 2018; Accepted: 11 January 2019; Published: 14 January 2019 Abstract: Natural killer (NK) cells are innate immune cells that can be activated rapidly to target abnormal and virus-infected cells without prior sensitization. With significant advancements in cell biology technologies, many NK cell lines have been established. Among these cell lines, NK-92 cells are not only the most widely used but have also been approved for clinical applications. Additionally, chimeric antigen receptor-modified NK-92 cells (CAR-NK-92 cells) have shown strong antitumor effects. In this review, we summarize established human NK cell lines and their biological characteristics, and highlight the applications of NK-92 cells and CAR-NK-92 cells in tumor immunotherapy. Keywords: natural killer cell line; NK-92; chimeric antigen receptor; immunotherapy; tumor 1. Introduction Natural killer (NK) cells are innate immune cells that were first discovered in mice in 1975 [1]. NK cells account for approximately 10% of lymphocytes in human peripheral blood (PB). Owing to the distinct chemokine receptors expressed in NK cells, the distributions of NK cells differ among healthy tissues. Most NK cells are found in the PB, liver, spleen, and bone marrow, and a small portion are also present in the lymph nodes [2–5]. -
PAX5 Expression in Acute Leukemias: Higher B-Lineage Specificity Than Cd79a and Selective Association with T(8;21)-Acute Myelogenous Leukemia
[CANCER RESEARCH 64, 7399–7404, October 15, 2004] PAX5 Expression in Acute Leukemias: Higher B-Lineage Specificity Than CD79a and Selective Association with t(8;21)-Acute Myelogenous Leukemia Enrico Tiacci,1 Stefano Pileri,2 Annette Orleth,1 Roberta Pacini,1 Alessia Tabarrini,1 Federica Frenguelli,1 Arcangelo Liso,3 Daniela Diverio,4 Francesco Lo-Coco,5 and Brunangelo Falini1 1Institutes of Hematology and Internal Medicine, University of Perugia, Perugia, Italy; 2Unit of Hematopathology, University of Bologne, Bologne, Italy; 3Section of Hematology, University of Foggia, Foggia, Italy; 4Department of Cellular Biotechnologies and Hematology, University La Sapienza of Rome, Rome, Italy; and 5Department of Biopathology, University Tor Vergata of Rome, Rome, Italy ABSTRACT (13, 16). PAX5 expression also occurs in the adult testis and in the mesencephalon and spinal cord during embryogenesis (17), suggesting an The transcription factor PAX5 plays a key role in the commitment of important role in the development of these tissues. hematopoietic precursors to the B-cell lineage, but its expression in acute Rearrangement of the PAX5 gene through reciprocal chromosomal leukemias has not been thoroughly investigated. Hereby, we analyzed routine biopsies from 360 acute leukemias of lymphoid (ALLs) and mye- translocations has been described in different types of B-cell malig- loid (AMLs) origin with a specific anti-PAX5 monoclonal antibody. Blasts nancies (18–23), and, more recently, PAX5 has also been shown to be from 150 B-cell ALLs showed strong PAX5 nuclear expression, paralleling targeted by aberrant hypermutation in Ͼ50% of diffuse large B-cell that of CD79a in the cytoplasm. Conversely, PAX5 was not detected in 50 lymphomas (24). -
Human and Mouse CD Marker Handbook Human and Mouse CD Marker Key Markers - Human Key Markers - Mouse
Welcome to More Choice CD Marker Handbook For more information, please visit: Human bdbiosciences.com/eu/go/humancdmarkers Mouse bdbiosciences.com/eu/go/mousecdmarkers Human and Mouse CD Marker Handbook Human and Mouse CD Marker Key Markers - Human Key Markers - Mouse CD3 CD3 CD (cluster of differentiation) molecules are cell surface markers T Cell CD4 CD4 useful for the identification and characterization of leukocytes. The CD CD8 CD8 nomenclature was developed and is maintained through the HLDA (Human Leukocyte Differentiation Antigens) workshop started in 1982. CD45R/B220 CD19 CD19 The goal is to provide standardization of monoclonal antibodies to B Cell CD20 CD22 (B cell activation marker) human antigens across laboratories. To characterize or “workshop” the antibodies, multiple laboratories carry out blind analyses of antibodies. These results independently validate antibody specificity. CD11c CD11c Dendritic Cell CD123 CD123 While the CD nomenclature has been developed for use with human antigens, it is applied to corresponding mouse antigens as well as antigens from other species. However, the mouse and other species NK Cell CD56 CD335 (NKp46) antibodies are not tested by HLDA. Human CD markers were reviewed by the HLDA. New CD markers Stem Cell/ CD34 CD34 were established at the HLDA9 meeting held in Barcelona in 2010. For Precursor hematopoetic stem cell only hematopoetic stem cell only additional information and CD markers please visit www.hcdm.org. Macrophage/ CD14 CD11b/ Mac-1 Monocyte CD33 Ly-71 (F4/80) CD66b Granulocyte CD66b Gr-1/Ly6G Ly6C CD41 CD41 CD61 (Integrin b3) CD61 Platelet CD9 CD62 CD62P (activated platelets) CD235a CD235a Erythrocyte Ter-119 CD146 MECA-32 CD106 CD146 Endothelial Cell CD31 CD62E (activated endothelial cells) Epithelial Cell CD236 CD326 (EPCAM1) For Research Use Only. -
Bispecific CAR-T Cells Targeting Both CD19 and CD22 for Therapy Of
Dai et al. Journal of Hematology & Oncology (2020) 13:30 https://doi.org/10.1186/s13045-020-00856-8 RAPID COMMUNICATION Open Access Bispecific CAR-T cells targeting both CD19 and CD22 for therapy of adults with relapsed or refractory B cell acute lymphoblastic leukemia Hanren Dai1,2,3†, Zhiqiang Wu1†, Hejin Jia2†, Chuan Tong1, Yelei Guo1, Dongdong Ti1, Xiao Han1, Yang Liu4, Wenying Zhang2, Chunmeng Wang2, Yajing Zhang2, Meixia Chen2, Qingming Yang2, Yao Wang1* and Weidong Han1,2* Abstract Background: Despite the impressive complete remission (CR) induced by CD19 CAR-T cell therapy in B-ALL, the high rate of complete responses is sometimes limited by the emergence of CD19-negative leukemia. Bispecific CAR-modified T cells targeting both CD19 and CD22 may overcome the limitation of CD19-negative relapse. Methods: We here report the design of a bispecific CAR simultaneous targeting of CD19 and CD22. We performed a phase 1 trial of bispecific CAR T cell therapy in patients with relapsed/refractory precursor B-ALL at a dose that ranged from 1.7 × 106 to 3 × 106 CAR T cells per kilogram of body weight. Results: We demonstrate bispecific CD19/CD22 CAR T cells could trigger robust cytolytic activity against target cells. MRD-negative CR was achieved in 6 out of 6 enrolled patients. Autologous CD19/CD22 CAR T cells proliferated in vivo and were detected in the blood, bone marrow, and cerebrospinal fluid. No neurotoxicity occurred in any of the 6 patients treated. Of note, one patient had a relapse with blast cells that no longer expressed CD19 and exhibited diminished CD22 site density approximately 5 months after treatment. -
Antibody-Dependent Cellular Cytotoxicity Riiia and Mediate Γ
Effector Memory αβ T Lymphocytes Can Express Fc γRIIIa and Mediate Antibody-Dependent Cellular Cytotoxicity This information is current as Béatrice Clémenceau, Régine Vivien, Mathilde Berthomé, of September 27, 2021. Nelly Robillard, Richard Garand, Géraldine Gallot, Solène Vollant and Henri Vié J Immunol 2008; 180:5327-5334; ; doi: 10.4049/jimmunol.180.8.5327 http://www.jimmunol.org/content/180/8/5327 Downloaded from References This article cites 43 articles, 21 of which you can access for free at: http://www.jimmunol.org/content/180/8/5327.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 © 2008 by The American Association of Immunologists All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. The Journal of Immunology Effector Memory ␣ T Lymphocytes Can Express Fc␥RIIIa and Mediate Antibody-Dependent Cellular Cytotoxicity1 Be´atrice Cle´menceau,*† Re´gine Vivien,*† Mathilde Berthome´,*† Nelly Robillard,‡ Richard Garand,‡ Ge´raldine Gallot,*† Sole`ne Vollant,*† and Henri Vie´2*† Human memory T cells are comprised of distinct populations with different homing potential and effector functions: central memory T cells that mount recall responses to Ags in secondary lymphoid organs, and effector memory T cells that confer immediate protection in peripheral tissues. -
Epha Receptors and Ephrin-A Ligands Are Upregulated by Monocytic
Mukai et al. BMC Cell Biology (2017) 18:28 DOI 10.1186/s12860-017-0144-x RESEARCHARTICLE Open Access EphA receptors and ephrin-A ligands are upregulated by monocytic differentiation/ maturation and promote cell adhesion and protrusion formation in HL60 monocytes Midori Mukai, Norihiko Suruga, Noritaka Saeki and Kazushige Ogawa* Abstract Background: Eph signaling is known to induce contrasting cell behaviors such as promoting and inhibiting cell adhesion/ spreading by altering F-actin organization and influencing integrin activities. We have previously demonstrated that EphA2 stimulation by ephrin-A1 promotes cell adhesion through interaction with integrins and integrin ligands in two monocyte/ macrophage cell lines. Although mature mononuclear leukocytes express several members of the EphA/ephrin-A subclass, their expression has not been examined in monocytes undergoing during differentiation and maturation. Results: Using RT-PCR, we have shown that EphA2, ephrin-A1, and ephrin-A2 expression was upregulated in murine bone marrow mononuclear cells during monocyte maturation. Moreover, EphA2 and EphA4 expression was induced, and ephrin-A4 expression was upregulated, in a human promyelocytic leukemia cell line, HL60, along with monocyte differentiation toward the classical CD14++CD16− monocyte subset. Using RT-PCR and flow cytometry, we have also shown that expression levels of αL, αM, αX, and β2 integrin subunits were upregulated in HL60 cells along with monocyte differentiation while those of α4, α5, α6, and β1 subunits were unchanged. Using a cell attachment stripe assay, we have shown that stimulation by EphA as well as ephrin-A, likely promoted adhesion to an integrin ligand- coated surface in HL60 monocytes. Moreover, EphA and ephrin-A stimulation likely promoted the formation of protrusions in HL60 monocytes. -
AML Serum Mir-150 Mir-155 Mir-1246 Prog
Supplementary Table S1. Summary of current studies on EVs as biomarkers Disease Source Cargo Role Reference AML serum TGF-β1, CD34, Prognostic [21] CD33, CD117 AML serum miR-150 Prognostic [23] miR-155 miR-1246 AML serum miR-125b Prognostic [24] AML serum miR-10b Prognostic [25] CLL serum CD19, CD37 Prognostic [27] CLL plasma S100-A9 protein Prognostic [29] CLL plasma CD52 Prognostic [30] CLL plasma miR-150, miR-155, Diagnostic [31] miR-223, miR-29 CD37, CD9, CD63 CLL plasma mc-COX2 Prognostic [33] MF plasma CD61, CD62P Prognostic [34] MM serum CD38, CD138, Prognostic [37] CD44, CD147 MM serum let-7b and miR-18a Prognostic [40] nHL /HL plasma CD20/CD30 Diagnostic/Prognostic [20] Lymphoma plasma CD20 Prognostic [43] HL plasma miR-23p Diagnostic [44] miR-127-3p miR-21-5p miR-155-5p let-7a-5p Lymphoma plasma BCL-6 Prognostic [45] c-myc 1 Supplementary Table S2. Summary of current studies on EVs: re-education of the bone marrow niche Disease EV Target Cargo Functional effects Reference origin/Source AML AML cells MSC/stromal / Downregulating of KITL, [52] cells CXCL12, IGF1; Reducing support to normal hemopoiesis AML AML cells Stromal cells miR-155 Reducing secretion of [54] miR-375 cytokines and growth factor; miR-150 Affecting retention and differentiation of HSC in the bone marrow AML/MDS AML/MDS cells MSC miR-7977 Reducing the hemopoiesis [55] supportive capacity CLL CLL cells MSC miR-202-3p Promoting migration, [32] survival and proliferation CLL Plasma Stromal cells / Production of VEGF, [26] promoting survival of B cells CLL CLL cells -
List of Genes Used in Cell Type Enrichment Analysis
List of genes used in cell type enrichment analysis Metagene Cell type Immunity ADAM28 Activated B cell Adaptive CD180 Activated B cell Adaptive CD79B Activated B cell Adaptive BLK Activated B cell Adaptive CD19 Activated B cell Adaptive MS4A1 Activated B cell Adaptive TNFRSF17 Activated B cell Adaptive IGHM Activated B cell Adaptive GNG7 Activated B cell Adaptive MICAL3 Activated B cell Adaptive SPIB Activated B cell Adaptive HLA-DOB Activated B cell Adaptive IGKC Activated B cell Adaptive PNOC Activated B cell Adaptive FCRL2 Activated B cell Adaptive BACH2 Activated B cell Adaptive CR2 Activated B cell Adaptive TCL1A Activated B cell Adaptive AKNA Activated B cell Adaptive ARHGAP25 Activated B cell Adaptive CCL21 Activated B cell Adaptive CD27 Activated B cell Adaptive CD38 Activated B cell Adaptive CLEC17A Activated B cell Adaptive CLEC9A Activated B cell Adaptive CLECL1 Activated B cell Adaptive AIM2 Activated CD4 T cell Adaptive BIRC3 Activated CD4 T cell Adaptive BRIP1 Activated CD4 T cell Adaptive CCL20 Activated CD4 T cell Adaptive CCL4 Activated CD4 T cell Adaptive CCL5 Activated CD4 T cell Adaptive CCNB1 Activated CD4 T cell Adaptive CCR7 Activated CD4 T cell Adaptive DUSP2 Activated CD4 T cell Adaptive ESCO2 Activated CD4 T cell Adaptive ETS1 Activated CD4 T cell Adaptive EXO1 Activated CD4 T cell Adaptive EXOC6 Activated CD4 T cell Adaptive IARS Activated CD4 T cell Adaptive ITK Activated CD4 T cell Adaptive KIF11 Activated CD4 T cell Adaptive KNTC1 Activated CD4 T cell Adaptive NUF2 Activated CD4 T cell Adaptive PRC1 Activated -
T Cells the Usual Subsets
T cells: the usual subsets Chen Dong and Gustavo J. Martinez T cells have important roles in immune responses and function by directly secreting soluble mediators or important for adaptation of immune responses in different microenvironments and might be particularly through cell contact-dependent mechanisms. Many T cell subsets have been characterized. Although relevant for host defence against pathogens that colonize different tissues. Distinct T cell subsets, or effector T cells were originally considered to be terminally differentiated, a growing body of evidence has differentiation states, can be identified based on the cell surface markers expressed and/or the effector challenged this view and suggested that the phenotype of effector T cells is not completely fixed but is molecules produced by a particular T cell population. This Poster summarizes our current understanding of more flexible or plastic. T cells can have ‘mixed’ phenotypes (that is, have characteristics usually the surface markers, transcriptional regulators, effector molecules and functions of the different T cell associated with more than one T cell subset) and can interconvert from one subset phenotype to another, subsets that participate in immune responses. Further knowledge of how these T cell subsets are regulated IMMUNOLOGY although instructive signalling can lead to long-term fixation of cytokine memory. T cell plasticity can be and cooperate with each other will provide us with better tools to treat immune-related diseases. Cytotoxic T cell Exhausted T cell -
ORIGINAL ARTICLE Flow Cytometric Protein Expression Profiling As a Systematic Approach for Developing Disease-Specific Assays
Leukemia (2006) 20, 2102–2110 & 2006 Nature Publishing Group All rights reserved 0887-6924/06 $30.00 www.nature.com/leu ORIGINAL ARTICLE Flow cytometric protein expression profiling as a systematic approach for developing disease-specific assays: identification of a chronic lymphocytic leukaemia-specific assay for use in rituximab-containing regimens AC Rawstron, R de Tute, AS Jack and P Hillmen Haematological Malignancy Diagnostic Service (HMDS), Leeds Teaching Hospitals, Leeds, UK Depletion of disease below the levels detected by sensitive sustained remissions only occur in patients achieving an MRD- minimal residual disease (MRD) assays is associated with negative complete response.12 Therefore MRD is increasingly prolonged survival in chronic lymphocytic leukaemia (CLL). being used as an end point for therapeutic trials, and several Flow cytometric MRD assays are now sufficiently sensitive and rapid to guide the duration of therapy in CLL, but generally rely studies are now using the assessment of MRD to define the on assessment of CD20 expression, which cannot be accurately duration of therapy. measured during and after therapeutic approaches containing Approaches using allele-specific oligonucleotide polymerase rituximab. The aim of this study was to use analytical software chain reaction (ASO-PCR) to the immunoglobulin gene of the developed for microarray analysis to provide a systematic B-CLL cell are generally accepted to show the highest sensitivity approach for MRD flow assay development. Samples from CLL for MRD detection. However, more recent four-colour ap- patients (n ¼ 49), normal controls (n ¼ 21) and other B-lympho- proaches show sensitivities nearing that of ASO-PCR6,11,13 with proliferative disorders (n ¼ 12) were assessed with a panel of 66 antibodies. -
Review of Dendritic Cells, Their Role in Clinical Immunology, and Distribution in Various Animal Species
International Journal of Molecular Sciences Review Review of Dendritic Cells, Their Role in Clinical Immunology, and Distribution in Various Animal Species Mohammed Yusuf Zanna 1 , Abd Rahaman Yasmin 1,2,* , Abdul Rahman Omar 2,3 , Siti Suri Arshad 3, Abdul Razak Mariatulqabtiah 2,4 , Saulol Hamid Nur-Fazila 3 and Md Isa Nur Mahiza 3 1 Department of Veterinary Laboratory Diagnosis, Faculty of Veterinary Medicine, Universiti Putra Malaysia (UPM), Serdang 43400, Selangor, Malaysia; [email protected] 2 Laboratory of Vaccines and Biomolecules, Institute of Bioscience, Universiti Putra Malaysia (UPM), Serdang 43400, Selangor, Malaysia; [email protected] (A.R.O.); [email protected] (A.R.M.) 3 Department of Veterinary Pathology and Microbiology, Faculty of Veterinary Medicine, Universiti Putra Malaysia (UPM), Serdang 43400, Selangor, Malaysia; [email protected] (S.S.A.); [email protected] (S.H.N.-F.); [email protected] (M.I.N.M.) 4 Department of Cell and Molecular Biology, Faculty of Biotechnology and Biomolecular Science, Universiti Putra Malaysia (UPM), Serdang 43400, Selangor, Malaysia * Correspondence: [email protected]; Tel.: +603-8609-3473 or +601-7353-7341 Abstract: Dendritic cells (DCs) are cells derived from the hematopoietic stem cells (HSCs) of the bone marrow and form a widely distributed cellular system throughout the body. They are the most effi- cient, potent, and professional antigen-presenting cells (APCs) of the immune system, inducing and dispersing a primary immune response by the activation of naïve T-cells, and playing an important role in the induction and maintenance of immune tolerance under homeostatic conditions. Thus, this Citation: Zanna, M.Y.; Yasmin, A.R.; review has elucidated the general aspects of DCs as well as the current dynamic perspectives and Omar, A.R.; Arshad, S.S.; distribution of DCs in humans and in various species of animals that includes mouse, rat, birds, dog, Mariatulqabtiah, A.R.; Nur-Fazila, cat, horse, cattle, sheep, pig, and non-human primates. -
CD2 Molecules Redistribute to the Uropod During T Cell Scanning: Implications for Cellular Activation and Immune Surveillance
CD2 molecules redistribute to the uropod during T cell scanning: Implications for cellular activation and immune surveillance Elena V. Tibaldi*†, Ravi Salgia†‡, and Ellis L. Reinherz*†§ *Laboratory of Immunobiology and ‡Division of Adult Oncology, Lowe Center for Thoracic Oncology, Dana-Farber Cancer Institute, and †Department of Medicine, Harvard Medical School, Boston, MA 02115 Communicated by Stuart F. Schlossman, Dana-Farber Cancer Institute, Boston, MA, April 9, 2002 (received for review February 14, 2002) Dynamic binding between CD2 and CD58 counter-receptors on op- cells, whereas its counter-receptor CD58 is expressed on a posing cells optimizes immune recognition through stabilization of diverse array of nucleated and non-nucleated cells including cell–cell contact and juxtaposition of surface membranes at a distance APCs and stromal cells (reviewed in refs. 11 and 12). CD2 suitable for T cell receptor–ligand interaction. Digitized time-lapse functions in both T cell adhesion and activation processes (13). Ϸ differential interference contrast and immunofluorescence micros- Of note, the weak affinity of the CD2-CD58 interaction (Kd copy on living cells now show that this binding also induces T cell 1 M) is associated with remarkably fast on and off rates that polarization. Moreover, CD2 can facilitate motility of T cells along foster rapid and extensive exchange between CD2 and CD58 antigen-presenting cells via a movement referred to as scanning. Both partners on opposing cell surfaces (14–16). These biophysical activated CD4 and CD8 T cells are able to scan antigen-presenting cells characteristics are reminiscent of the selectin–ligand interactions surfaces in the absence of cognate antigen.