Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
  • Clinical Research and Public Health
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All ...
  • Videos
    • Conversations with Giants in Medicine
    • Video Abstracts
  • Reviews
    • View all reviews ...
    • Complement Biology and Therapeutics (May 2025)
    • Evolving insights into MASLD and MASH pathogenesis and treatment (Apr 2025)
    • Microbiome in Health and Disease (Feb 2025)
    • Substance Use Disorders (Oct 2024)
    • Clonal Hematopoiesis (Oct 2024)
    • Sex Differences in Medicine (Sep 2024)
    • Vascular Malformations (Apr 2024)
    • View all review series ...
  • Viewpoint
  • Collections
    • In-Press Preview
    • Clinical Research and Public Health
    • Research Letters
    • Letters to the Editor
    • Editorials
    • Commentaries
    • Editor's notes
    • Reviews
    • Viewpoints
    • 100th anniversary
    • Top read articles

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Video Abstracts
  • In-Press Preview
  • Clinical Research and Public Health
  • Research Letters
  • Letters to the Editor
  • Editorials
  • Commentaries
  • Editor's notes
  • Reviews
  • Viewpoints
  • 100th anniversary
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact

Citations to this article

EBNA1-specific CD4+ T cells in healthy carriers of Epstein-Barr virus are primarily Th1 in function
Kara Bickham, … , Nina Bhardwaj, Ralph Steinman
Kara Bickham, … , Nina Bhardwaj, Ralph Steinman
Published January 1, 2001
Citation Information: J Clin Invest. 2001;107(1):121-130. https://doi.org/10.1172/JCI10209.
View: Text | PDF
Article Article has an altmetric score of 3

EBNA1-specific CD4+ T cells in healthy carriers of Epstein-Barr virus are primarily Th1 in function

  • Text
  • PDF
Abstract

The Epstein-Barr virus (EBV) nuclear antigen-1 (EBNA1) maintains the viral episome in all host cells infected with EBV. Recently, EBNA1 was found to be the main EBV latency antigen for CD4+ T cells and could be recognized in cultures from all donors tested. We now identify a polarized Th1 phenotype and obtain evidence for its presence in vivo. When T cells were stimulated with dendritic cells infected with vaccinia vectors expressing EBNA1, 18 of 19 donors secreted IFN-γ, whereas only two of 19 secreted IL-4. Magnetic selection was then used to isolate cells from fresh blood based on EBNA1-induced cytokine production. Specific IFN-γ CD4+ cell lines were established from six of six donors and IL-4 lines from three of six. Only the Th1 lines specifically lysed targets expressing three different sources of EBNA1 protein. When the IgG isotype of EBNA1 plasma Ab’s was tested, most specific Ab’s were IgG1 and of a high titer, confirming a Th1 response to EBNA1 in vivo. Ab’s to other microbial antigens generally were not skewed toward IgG1. Given emerging evidence that Th1 CD4+ T cells have several critical roles in host defense to viral infection and tumors, we propose that EBNA1-specific CD4+ Th1 cells contribute to resistance to EBV and EBV-associated malignancies.

Authors

Kara Bickham, Christian Münz, Ming Li Tsang, Marie Larsson, Jean-Francois Fonteneau, Nina Bhardwaj, Ralph Steinman

×

Total citations by year

Year: 2023 2022 2021 2020 2019 2018 2017 2015 2014 2013 2012 2011 2010 2008 2007 2006 2005 2004 2003 2001 Total
Citations: 2 1 5 2 3 2 2 1 1 3 2 2 2 8 2 2 1 4 2 4 51
Citation information
This citation data is accumulated from CrossRef, which receives citation information from participating publishers, including this journal. Not all publishers participate in CrossRef, so this information is not comprehensive. Additionally, data may not reflect the most current citations to this article, and the data may differ from citation information available from other sources (for example, Google Scholar, Web of Science, and Scopus).

Citations to this article (51)

Title and authors Publication Year
mRNA-based Vaccines Targeting the T-cell Epitope-rich Domain of Epstein Barr Virus Latent Proteins Elicit Robust Anti-Tumor Immunity in Mice.
Zhao GX, Bu GL, Liu GF, Kong XW, Sun C, Li ZQ, Dai DL, Sun HX, Kang YF, Feng GK, Zhong Q, Zeng MS
2023
Circulating T follicular helper 2 cells, T follicular regulatory cells and regulatory B cells are effective biomarkers for predicting the response to house dust mite sublingual immunotherapy in patients with allergic respiratory diseases
Shigehara K, Kamekura R, Ikegami I, Sakamoto H, Yanagi M, Kamiya S, Kodama K, Asai Y, Miyajima S, Nishikiori H, Uno E, Yamamoto K, Takano K, Chiba H, Ohnishi H, Ichimiya S
Frontiers in immunology 2023
Epstein–Barr virus and multiple sclerosis
Soldan SS, Lieberman PM
Nature reviews. Microbiology 2022
Combining Antivirals and Immunomodulators to Fight COVID-19
V Feuillet, B Canard, A Trautmann
Trends in Immunology 2021
Immunophenotypic characterization of TCR γδ T cells and MAIT cells in HIV-infected individuals developing Hodgkin’s lymphoma
CK Muller, J Spagnuolo, A Audigé, A Chancellor, D Russenberger, AU Scherrer, M Hoffmann, R Kouyos, M Battegay, GD Libero, RF Speck
Infectious agents and cancer 2021
Burkitt lymphoma with a granulomatous reaction: an M1/Th1‐polarised microenvironment is associated with controlled growth and spontaneous regression
M Granai, S Lazzi, V Mancini, A Akarca, R Santi, F Vergoni, E Sorrentino, R Guazzo, L Mundo, G Cevenini, C Tripodo, GD Stefano, B Puccini, M Ponzoni, E Sabattini, C Agostinelli, N Bassüllü, T Tecimer, AS Demiroz, L Mnango, S Dirnhofer, L QuintanillaMartinez, T Marafioti, F Fend, L Leoncini
Histopathology 2021
Variances in Antiviral Memory T-Cell Repertoire of CD45RA- and CD62L-Depleted Lymphocyte Products Reflect the Need of Individual T-Cell Selection Strategies to Reduce the Risk of GvHD while Preserving Antiviral Immunity in Adoptive T-Cell Therapy
Mangare C, Tischer-Zimmermann S, Bonifacius A, Riese SB, Dragon AC, Blasczyk R, Maecker-Kolhoff B, Eiz-Vesper B
Transfusion Medicine and Hemotherapy 2021
Guidelines for the use of flow cytometry and cell sorting in immunological studies (third edition).
Cossarizza A, Chang HD, Radbruch A, Abrignani S, Addo R, Akdis M, Andrä I, Andreata F, Annunziato F, Arranz E, Bacher P, Bari S, Barnaba V, Barros-Martins J, Baumjohann D, Beccaria CG, Bernardo D, Boardman DA, Borger J, Böttcher C, Brockmann L, Burns M, Busch DH, Cameron G, Cammarata I, Cassotta A, Chang Y, Chirdo FG, Christakou E, Čičin-Šain L, Cook L, Corbett AJ, Cornelis R, Cosmi L, Davey MS, De Biasi S, De Simone G, Del Zotto G, Delacher M, Di Rosa F, Di Santo J, Diefenbach A, Dong J, Dörner T, Dress RJ, Dutertre CA, Eckle SBG, Eede P, Evrard M, Falk CS, Feuerer M, Fillatreau S, Fiz-Lopez A, Follo M, Foulds GA, Fröbel J, Gagliani N, Galletti G, Gangaev A, Garbi N, Garrote JA, Geginat J, Gherardin NA, Gibellini L, Ginhoux F, Godfrey DI, Gruarin P, Haftmann C, Hansmann L, Harpur CM, Hayday AC, Heine G, Hernández DC, Herrmann M, Hoelsken O, Huang Q, Huber S, Huber JE, Huehn J, Hundemer M, Hwang WYK, Iannacone M, Ivison SM, Jäck HM, Jani PK, Keller B, Kessler N, Ketelaars S, Knop L, Knopf J, Koay HF, Kobow K, Kriegsmann K, Kristyanto H, Krueger A, Kuehne JF, Kunze-Schumacher H, Kvistborg P, Kwok I, Latorre D, Lenz D, Levings MK, Lino AC, Liotta F, Long HM, Lugli E, MacDonald KN, Maggi L, Maini MK, Mair F, Manta C, Manz RA, Mashreghi MF, Mazzoni A, McCluskey J, Mei HE, Melchers F, Melzer S, Mielenz D, Monin L, Moretta L, Multhoff G, Muñoz LE, Muñoz-Ruiz M, Muscate F, Natalini A, Neumann K, Ng LG, Niedobitek A, Niemz J, Almeida LN, Notarbartolo S, Ostendorf L, Pallett LJ, Patel AA, Percin GI, Peruzzi G, Pinti M, Pockley AG, Pracht K, Prinz I, Pujol-Autonell I, Pulvirenti N, Quatrini L, Quinn KM, Radbruch H, Rhys H, Rodrigo MB, Romagnani C, Saggau C, Sakaguchi S, Sallusto F, Sanderink L, Sandrock I, Schauer C, Scheffold A, Scherer HU, Schiemann M, Schildberg FA, Schober K, Schoen J, Schuh W, Schüler T, Schulz AR, Schulz S, Schulze J, Simonetti S, Singh J, Sitnik KM, Stark R, Starossom S, Stehle C, Szelinski F, Tan L, Tarnok A, Tornack J, Tree TIM, van Beek JJP, van de Veen W, van Gisbergen K, Vasco C, Verheyden NA, von Borstel A, Ward-Hartstonge KA, Warnatz K, Waskow C, Wiedemann A, Wilharm A, Wing J, Wirz O, Wittner J, Yang JHM, Yang J
European Journal of Immunology 2021
Immunology of EBV-Related Lymphoproliferative Disease in HIV-Positive Individuals
P Shindiapina, EH Ahmed, A Mozhenkova, T Abebe, RA Baiocchi
Frontiers in Oncology 2020
Prognostic Significance of Granuloma and Amyloid Deposition in Nasopharyngeal Carcinoma
YC Lee, LY Lee, NM Tsang, CL Hsu, LJ Hsin, T Kuo, KP Chang
Head and Neck Pathology 2020
Infection and immune control of human oncogenic γ-herpesviruses in humanized mice
D McHugh, N Caduff, A Murer, C Engelmann, Y Deng, H Zdimerova, K Zens, O Chijioke, C Münz
Philosophical Transactions of the Royal Society B: Biological Sciences 2019
Correction: Absence of anti-hypocretin receptor 2 autoantibodies in post pandemrix narcolepsy cases
G Luo, L Lin, L Jacob, M Bonvalet, A Ambati, G Plazzi, F Pizza, R Leib, CM Adams, M Partinen, EJ Mignot
PloS one 2019
Primary EBV Infection Induces an Acute Wave of Activated Antigen-Specific Cytotoxic CD4 + T Cells
BJ Meckiff, K Ladell, JE McLaren, GB Ryan, AM Leese, EA James, DA Price, HM Long
Journal of immunology (Baltimore, Md. : 1950) 2019
Immunogenic particles with a broad antigenic spectrum stimulate cytolytic T cells and offer increased protection against EBV infection ex vivo and in mice
DG van Zyl, MH Tsai, A Shumilov, V Schneidt, R Poirey, B Schlehe, H Fluhr, J Mautner, HJ Delecluse, R Khanna
PLoS pathogens 2018
CMV and EBV targets recognized by tumor-infiltrating B lymphocytes in pancreatic cancer and brain tumors
Q Meng, D Valentini, M Rao, E Dodoo, M Maeurer
Scientific Reports 2018
Fighting Viral Infections and Virus-Driven Tumors with Cytotoxic CD4+ T Cells
E Muraro, A Merlo, D Martorelli, M Cangemi, SD Santa, R Dolcetti, A Rosato
Frontiers in immunology 2017
Epstein-Barr Virus as a Promising Immunotherapeutic Target for Nasopharyngeal Carcinoma Treatment
SY Teow, HY Yap, SC Peh
Journal of Pathogens 2017
Measurement of CD8+ and CD4+ T Cell Frequencies Specific for EBV LMP1 and LMP2a Using mRNA-Transfected DCs
DH Sohn, HJ Sohn, HJ Lee, SD Lee, S Kim, SJ Hyun, HI Cho, SG Cho, SK Lee, TG Kim, JS Pagano
PloS one 2015
A complex role of herpes viruses in the disease process of multiple sclerosis
SC Wuest, I Mexhitaj, NR Chai, E Romm, J Scheffel, B Xu, K Lane, T Wu, B Bielekova
PloS one 2014
MHC II tetramers visualize human CD4+ T cell responses to Epstein-Barr virus infection and demonstrate atypical kinetics of the nuclear antigen EBNA1 response
HM Long, OL Chagoury, AM Leese, GB Ryan, E James, LT Morton, RJ Abbott, S Sabbah, W Kwok, AB Rickinson
Journal of Experimental Medicine 2013
CD4+ and CD8+ T-cell responses to latent antigen EBNA-1 and lytic antigen BZLF-1 during persistent lymphocryptovirus infection of rhesus macaques
RM Leskowitz, XY Zhou, F Villinger, MH Fogg, A Kaur, PM Lieberman, F Wang, HC Ertl
Journal of virology 2013
Therapeutic vaccination against the rhesus lymphocryptovirus EBNA-1 homologue, rhEBNA-1, elicits T cell responses to novel epitopes in rhesus macaques
EL Silveira, MH Fogg, RM Leskowitz, HC Ertl, RW Wiseman, DH O'Connor, P Lieberman, F Wang, F Villinger
Journal of virology 2013
Rapidly Generated Multivirus-specific Cytotoxic T Lymphocytes for the Prophylaxis and Treatment of Viral Infections
U Gerdemann, JM Keirnan, UL Katari, R Yanagisawa, AS Christin, LE Huye, SK Perna, S Ennamuri, S Gottschalk, MK Brenner, HE Heslop, CM Rooney, AM Leen
Molecular Therapy 2012
Enhancing cancer immunotherapy by intracellular delivery of cell-penetrating peptides and stimulation of pattern-recognition receptor signaling
HY Wang, RF Wang
Advances in immunology 2012
Distinct roles of CD4+ T cell subpopulations in retroviral immunity: lessons from the Friend virus mouse model
S Nair, W Bayer, MJ Ploquin, G Kassiotis, KJ Hasenkrug, U Dittmer
Retrovirology 2011
Generation of Multivirus-specific T Cells to Prevent/treat Viral Infections after Allogeneic Hematopoietic Stem Cell Transplant
U Gerdemann, JF Vera, CM Rooney, AM Leen
Journal of visualized experiments : JoVE 2011
Prospects of a novel vaccination strategy for human gamma-herpesviruses
TT Wu, MA Blackman, R Sun
Immunologic Research 2010
Persistent γ-Herpesvirus Infection Induces a CD4 T Cell Response Containing Functionally Distinct Effector Populations
KA Stuller, SS Cush, E Flaño
Journal of immunology (Baltimore, Md. : 1950) 2010
Targeting the nuclear antigen 1 of Epstein-Barr virus to the human endocytic receptor DEC-205 stimulates protective T-cell responses
C Gurer, T Strowig, F Brilot, M Pack, C Trumpfheller, F Arrey, CG Park, RM Steinman, C Münz
Blood 2008
Tonsilar NK cells restrict B cell transformation by the Epstein-Barr virus via IFN-gamma
T Strowig, F Brilot, F Arrey, G Bougras, D Thomas, WA Muller, C Münz
PLoS pathogens 2008
EBNA1-specific T cells from patients with multiple sclerosis cross react with myelin antigens and co-produce IFN-gamma and IL-2
JD Lünemann, I Jelcić, S Roberts, A Lutterotti, B Tackenberg, R Martin, C Münz
Journal of Experimental Medicine 2008
The cytolytic enzymes granyzme A, granzyme B, and perforin: expression patterns, cell distribution, and their relationship to cell maturity and bright CD57 expression
PK Chattopadhyay, MR Betts, DA Price, E Gostick, H Horton, M Roederer, SC de Rosa
Journal of leukocyte biology 2008
Immune escape by Epstein-Barr virus associated malignancies
C Münz, A Moormann
Seminars in Cancer Biology 2008
Broadened and elevated humoral immune response to EBNA1 in pediatric multiple sclerosis
JD Lünemann, P Huppke, S Roberts, W Brück, J Gärtner, C Münz
Neurology 2008
Patients with Epstein Barr virus-positive lymphomas have decreased CD4(+) T-cell responses to the viral nuclear antigen 1
KN Heller, F Arrey, P Steinherz, C Portlock, A Chadburn, K Kelly, C Münz
International Journal of Cancer 2008
Increased Frequency of EBV-Specific Effector Memory CD8+ T Cells Correlates with Higher Viral Load in Rheumatoid Arthritis
Lünemann JD, Frey O, Eidner T, Baier M, Roberts S, Sashihara J, Volkmer R, Cohen JI, Hein G, Kamradt T, Münz C
Journal of immunology (Baltimore, Md. : 1950) 2008
Primary CD4+ T-Cell Responses Provide both Helper and Cytotoxic Functions during Epstein-Barr Virus Infection and Transformation of Fetal Cord Blood B Cells
GJ MacArthur, AD Wilson, MA Birchall, AJ Morgan
Journal of virology 2007
Epstein-Barr Virus: Environmental Trigger of Multiple Sclerosis?
JD Lünemann, T Kamradt, R Martin, C Münz
Journal of virology 2007
Acquisition of direct antiviral effector functions by CMV-specific CD4 + T lymphocytes with cellular maturation
JP Casazza, MR Betts, DA Price, ML Precopio, LE Ruff, JM Brenchley, BJ Hill, M Roederer, DC Douek, RA Koup
Journal of Experimental Medicine 2006
Distinct memory CD4+ T-cell subsets mediate immune recognition of Epstein Barr virus nuclear antigen 1 in healthy virus carriers
KN Heller, J Upshaw, B Seyoum, H Zebroski, C Münz
Blood 2006
Immune Regulation of Viral Infection and Vice Versa
HW Virgin
Immunologic Research 2005
Critical Role of EBNA1-Specific CD4+ T Cells in the Control of Burkitt’s Lymphoma in vivo
Tihui Fu, Kuishin Voo and Rong-Fu Wang
Journal of Clinical Investigation 2004
An optimized CD4 T-cell response can control productive and latent gammaherpesvirus infection
RL Sparks-Thissen, DC Braaten, S Kreher, SH Speck, HW 4th
Journal of virology 2004
Epstein-Barr Virus Nuclear Antigen 1: Figure 1.: from Immunologically Invisible to a Promising T Cell Target
C Münz
Journal of Experimental Medicine 2004
Identification of a Protective CD4 + T-Cell Epitope in p15 gag of Friend Murine Leukemia Virus and Role of the MA Protein Targeting the Plasma Membrane in Immunogenicity
D Sugahara, S Tsuji-Kawahara, M Miyazawa
Journal of virology 2004
Dendritic cells initiate immune control of epstein-barr virus transformation of B lymphocytes in vitro
K Bickham, K Goodman, C Paludan, S Nikiforow, ML Tsang, RM Steinman, C Münz
Journal of Experimental Medicine 2003
Cytolytic CD4 + -T-Cell Clones Reactive to EBNA1 Inhibit Epstein-Barr Virus-Induced B-Cell Proliferation
S Nikiforow, K Bottomly, G Miller, C Münz
Journal of virology 2003
In vitro cytokine production and growth inhibition of lymphoblastoid cell lines by CD4+ T cells from Epstein-Barr virus (EBV) seropositive donors
AD Wilson, JC Hopkins, AJ Morgan
Clinical & Experimental Immunology 2001
Multiple Effector Functions Mediated by Human Immunodeficiency Virus-Specific CD4 + T-Cell Clones
PJ Norris, M Sumaroka, C Brander, HF Moffett, SL Boswell, T Nguyen, Y Sykulev, BD Walker, ES Rosenberg
Journal of virology 2001
Differential Immunogenicity of Epstein-Barr Virus Latent-Cycle Proteins for Human CD4 + T-Helper 1 Responses
A Leen, P Meij, I Redchenko, J Middeldorp, E Bloemena, A Rickinson, N Blake
Journal of virology 2001
Dendritic Cells Cross-Present Latency Gene Products from Epstein-Barr Virus–Transformed B Cells and Expand Tumor-Reactive Cd8+ Killer T Cells
Subklewe M, Paludan C, Tsang ML, Mahnke K, Steinman RM, Münz C
Journal of Experimental Medicine 2001

← Previous 1 2 3 Next →

Advertisement

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts

Referenced in 2 patents
34 readers on Mendeley
See more details