In vitro T cell responses to a candidate Epstein-Barr virus vaccine: human CD4+ T cell clones specific for the major envelope glycoprotein gp340

1988 ◽  
Vol 18 (11) ◽  
pp. 1689-1698 ◽  
Author(s):  
David Ulaeto ◽  
Lesley Waace ◽  
Andrew Morgan ◽  
Bror Morein ◽  
Alan B. Rickinson
Keyword(s):  
T Cell ◽  
Virus Vaccine ◽  
Envelope Glycoprotein ◽  
Epstein Barr Virus ◽  
Cd4 T Cell ◽  
Barr Virus ◽  
Cell Responses ◽  
Cell Clones ◽  
Epstein Barr

CD4+ T-cell clones recognizing human lymphoma-associated antigens: generation by in vitro stimulation with autologous Epstein-Barr virus–transformed B cells

Blood ◽  
2009 ◽  
Vol 114 (4) ◽  
pp. 807-815 ◽  
Author(s):  
Heather M. Long ◽  
Jianmin Zuo ◽  
Alison M. Leese ◽  
Nancy H. Gudgeon ◽  
Hui Jia ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Epstein Barr Virus ◽  
Hla Class Ii ◽  
Cd4 T Cell ◽  
T Cell Clones ◽  
Barr Virus ◽  
Cell Clones ◽  
Epstein Barr

Abstract Epstein-Barr virus (EBV)–specific T-cell preparations, generated by stimulating immune donor lymphocytes with the autologous virus-transformed B-lymphoblastoid cell line (LCL) in vitro, can be used to target EBV-positive malignancies. Although these preparations are enriched for EBV antigen–specific CD8+ T cells, most also contain a CD4+ T-cell population whose specificity is unknown. Here, we show that, although CD4+ T-cell clones derived from such cultures recognize HLA class II–matched LCLs but not mitogen-activated B lymphoblasts, many (1) do not map to any known EBV antigen, (2) can be raised from EBV-naive as well as EBV-immune persons, and (3) can recognize a broad range of human B lymphoma–derived cell lines irrespective of EBV genome status, providing those lines to express the relevant HLA class II–restricting allele. Importantly, such CD4+ clones not only produce IFNγ but are also cytotoxic and can control the outgrowth of HLA-matched lymphoma cells in cocultivation assays. We infer that such CD4+ T cells recognize cellular antigens that are preferentially up-regulated in EBV-transformed but not mitogen-activated B lymphoblasts and that are also expressed in a range of B-cell malignancies. Such antigens are therefore of potential value as targets for CD4+ T cell–based immunotherapy.

scholarly journals Epstein-Barr Virus Evades CD4+ T Cell Responses in Lytic Cycle through BZLF1-mediated Downregulation of CD74 and the Cooperation of vBcl-2

2011 ◽  
Vol 7 (12) ◽  
pp. e1002455 ◽  
Author(s):  
Jianmin Zuo ◽  
Wendy A. Thomas ◽  
Tracey A. Haigh ◽  
Leah Fitzsimmons ◽  
Heather M. Long ◽  
...  
Keyword(s):  
T Cell ◽  
Epstein Barr Virus ◽  
T Cell Responses ◽  
Lytic Cycle ◽  
Cd4 T Cell ◽  
Barr Virus ◽  
Cell Responses ◽  
Epstein Barr

scholarly journals Differential Immunogenicity of Epstein-Barr Virus Latent-Cycle Proteins for Human CD4+ T-Helper 1 Responses

2001 ◽  
Vol 75 (18) ◽  
pp. 8649-8659 ◽  
Author(s):  
Ann Leen ◽  
Pauline Meij ◽  
Irina Redchenko ◽  
Jaap Middeldorp ◽  
Elisabeth Bloemena ◽  
...  
Keyword(s):  
T Cell ◽  
Epstein Barr Virus ◽  
T Helper ◽  
Antigen Specificity ◽  
T Helper 1 ◽  
Barr Virus ◽  
Cell Responses ◽  
Nuclear Antigens ◽  
Epstein Barr

ABSTRACT Human CD4+ T-helper 1 cell responses to Epstein-Barr virus (EBV) infection are likely to be important in the maintenance of virus-specific CD8+ memory and/or as antiviral effectors in their own right. The present work has used overlapping peptides as stimulators of gamma interferon release (i) to identify CD4+ epitopes within four EBV latent-cycle proteins, i.e., the nuclear antigens EBNA1 and EBNA3C and the latent membrane proteins LMP1 and LMP2, and (ii) to determine the frequency and magnitude of memory responses to these proteins in healthy virus carriers. Responses to EBNA1 and EBNA3C epitopes were detected in the majority of donors, and in the case of EBNA1, their antigen specificity was confirmed by in vitro reactivation and cloning of CD4+ T cells using protein-loaded dendritic cell stimulators. By contrast, responses to LMP1 and LMP2 epitopes were seen much less frequently. EBV latent-cycle proteins therefore display a marked hierarchy of immunodominance for CD4+ T-helper 1 cells (EBNA1, EBNA3C ≫ LMP1, LMP2) which is different from that identified for the same proteins with respect to CD8+-T-cell responses (EBNA3C > EBNA1 > LMP2 ≫ LMP1). Furthermore, the range of CD4+ memory T-cell frequencies in peripheral blood of healthy virus carriers was noticeably lower and narrower than the corresponding range of latent antigen-specific CD8+-T-cell frequencies.

scholarly journals Differential Targeting and Shifts in the Immunodominance of Epstein‐Barr Virus–Specific CD8 and CD4 T Cell Responses during Acute and Persistent Infection

2005 ◽  
Vol 192 (9) ◽  
pp. 1513-1524 ◽  
Author(s):  
Tonia Woodberry ◽  
Todd J. Suscovich ◽  
Leah M. Henry ◽  
Jennifer K. Davis ◽  
Nicole Frahm ◽  
...  
Keyword(s):  
T Cell ◽  
Persistent Infection ◽  
Epstein Barr Virus ◽  
T Cell Responses ◽  
Cd4 T Cell ◽  
Barr Virus ◽  
Cell Responses ◽  
Epstein Barr ◽  
And Shifts

scholarly journals Galectin-1 mediated suppression of Epstein-Barr virus–specific T-cell immunity in classic Hodgkin lymphoma

Blood ◽  
2007 ◽  
Vol 110 (4) ◽  
pp. 1326-1329 ◽  
Author(s):  
Maher K. Gandhi ◽  
Guido Moll ◽  
Corey Smith ◽  
Ujjwal Dua ◽  
Eleanore Lambley ◽  
...  
Keyword(s):  
T Cell ◽  
Hodgkin Lymphoma ◽  
Epstein Barr Virus ◽  
T Cell Responses ◽  
Cd8 T Cell ◽  
Barr Virus ◽  
Cell Responses ◽  
Cell Immunity ◽  
Epstein Barr

AbstractIn Hodgkin lymphoma (HL), the malignant Hodgkin Reed-Sternberg cells interact with the host microenvironment to create an immunosuppressive network that protects the lymphoma from immune attack. These mechanisms are not fully understood. We examined the role of the immunomodulatory protein galectin-1 (Gal-1) on Epstein-Barr virus-specific CD8+ T cell responses in HL. Initial studies indicated Gal-1 expression in all in vitro established Hodgkin Reed-Sternberg cell lines. In situ analysis revealed Gal-1 expression in 26 of 42 classic HL, whereas Gal-1 was uniformly negative in nodular lymphocyte predominant HL. Gal-1hi expression was associated with male gender, older patients, reduced CD8+ T cell infiltration at the tumor site, and most importantly, an impaired latent membrane protein 1 and 2-specific CD8+ T-cell responses. In vitro exposure to recombinant Gal-1 inhibited proliferation and interferon-γ expression by Epstein-Barr virus-specific T cells. These observations provide an important link between the Gal-1-mediated immunomodulatory networks and loss of antigen-specific T-cell function in classic HL.

scholarly journals CD4 + T cells are found within endemic Burkitt lymphoma and modulate Burkitt lymphoma precursor cell viability and expression of pathogenically relevant Epstein–Barr virus genes

2021 ◽  
Author(s):  
Semjon Sidorov ◽  
Lara Fux ◽  
Katja Steiner ◽  
Samyo Bounlom ◽  
Sabrina Traxel ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Burkitt Lymphoma ◽  
Cd4 T Cells ◽  
Epstein Barr Virus ◽  
Cell Cancer ◽  
Cd4 T Cell ◽  
Barr Virus ◽  
Epstein Barr

AbstractEndemic Burkitt lymphoma (eBL) is an aggressive B cell cancer characterized by an IgH/c-myc translocation and the harboring of Epstein–Barr virus (EBV). Evidence accumulates that CD4 + T cells might contribute to eBL pathogenesis. Here, we investigate the presence of CD4 + T cells in primary eBL tissue and their potential dichotomous impact on an EBV-infected pre-eBL cell model using ex vivo material and in vitro co-cultures. In addition, we establish a novel method to study the effect of IgH/c-myc translocation in primary B cells by employing a CRISPR/Cas9 knock-in approach to introduce and tag de novo translocation. We unprecedently document that CD4 + T cells are present in primary eBL tumor tissue. Furthermore, we demonstrate that CD4 + T cells on the one hand suppress eBL development by killing pre-eBL cells lacking IgH/c-myc translocation in vitro and on the other hand indirectly promote eBL development by inducing crucial EBV Latency III to Latency I switching in pre-eBL cells. Finally, we show that while the mere presence of an IgH/c-myc translocation does not suffice to escape CD4 + T-cell-mediated killing in vitro, the CD4 + T-cell-mediated suppression of EBV’s Latency III program in vivo may allow cells harboring an IgH/c-myc translocation and additional mutations to evade immune control and proliferate by means of deregulated c-myc activity, resulting in neoplasia. Thus, our study highlights the dichotomous effects of CD4 + T cells and the mechanisms involved in eBL pathogenesis, suggests mechanisms of their impact on eBL progression, and provides a novel in vitro model for further investigation of IgH/c-myc translocation.

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