Long-term T-cell-mediated immunity to epstein-barr virus in man. I. Complete regression of virus-induced transformation in cultures of seropositive donor leukocytes

1978 ◽  
Vol 22 (6) ◽  
pp. 662-668 ◽  
Author(s):  
D. J. Moss ◽  
A. B. Rickinson ◽  
J. H. Pope
Keyword(s):  
T Cell ◽  
Epstein Barr Virus ◽  
Cell Mediated Immunity ◽  
Complete Regression ◽  
Barr Virus ◽  
Epstein Barr

Studies on long-term T-cell-mediated immunity to epstein-barr virus in immunosuppressed renal allograft recipients

1981 ◽  
Vol 28 (6) ◽  
pp. 705-709 ◽  
Author(s):  
D. H. Crawford ◽  
J. M. B. Edwards ◽  
P. Sweny ◽  
A. V. Hoffbrand ◽  
G. Janossy
Keyword(s):  
T Cell ◽  
Epstein Barr Virus ◽  
Renal Allograft ◽  
Cell Mediated Immunity ◽  
Barr Virus ◽  
Epstein Barr

LONG-TERM T-CELL-MEDIATED IMMUNITY TO EPSTEIN-BARR VIRUS IN RENAL-ALLOGRAFT RECIPIENTS RECEIVING CYCLOSPORIN A

The Lancet ◽  
1981 ◽  
Vol 317 (8210) ◽  
pp. 10-13 ◽  
Author(s):  
DorothyH. Crawford ◽  
JoanM.B. Edwards ◽  
Paul Sweny ◽  
George Janossy ◽  
A.Victor Hoffbrand
Keyword(s):  
T Cell ◽  
Cyclosporin A ◽  
Epstein Barr Virus ◽  
Renal Allograft ◽  
Cell Mediated Immunity ◽  
Barr Virus ◽  
Epstein Barr

scholarly journals Pembrolizumab Therapy Exacerbates EBV-Induced Infections and Tumors in a Long-Term Fully Humanized Mouse Model

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 2405-2405
Author(s):  
Renata Stripecke ◽  
Simon Danisch ◽  
Constanze Slabik ◽  
Reinhard Zeidler ◽  
Wolfgang Hammerschmidt ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd8 T Cells ◽  
Epstein Barr Virus ◽  
Humanized Mouse ◽  
Humanized Mouse Model ◽  
Barr Virus ◽  
Ebv Infection ◽  
Epstein Barr

Abstract INTRODUCTION: A promising rich pipeline of combination therapies targeting checkpoint molecules expressed on T cells and/or tumor cells is currently being developed to abrogate tumor-induced immunosuppression. Novel in vivo models suitable for validating these immunotherapies and predict safety issues are warranted to accelerate their translation to patients. AIM: Epstein Barr virus (EBV) is a type 1 carcinogen that is directly associated with the development of human B cell neoplasms. We modelled EBV infection and tumor progression in long-term humanized mice and investigated the activation of T cells with PD-1 expression. Further, we performed studies evaluating the effects of an anti-PD-1 antibody (pembrolizumab/ keytruda) in on EBV infections and/or tumor growth. METHODS: Humanized mice transplanted with human cord-blood CD34+ stem cells and showing long-term (15 weeks) human T cell reconstitution were infected with an oncogenic recombinant Epstein Barr Virus (EBV), encoding enhanced firefly luciferase (fLuc) and green fluorescent protein (GFP). EBV infections were monitored by optical imaging analyses and PCR. CD8+ and CD4+ T cell subtypes (PD-1+, naïve, central memory, effector memory and terminal effector) were sequentially monitored in blood by longitudinal flow cytometry analyses and in organs at experimental endpoint. Histopathological analyses were performed to characterize EBV infection (EBER+) and PD-1+ T cell-rich infiltrates in tissues and tumors. We used the model to evaluate the effects of pembrolizumab administered after EBV challenge at low dose (first dose 1.65mg/kg and then 3.30 mg/kg, every other week, n=3) or high dose (first dose 5.00 mg/kg and then 10.00 mg/kg every other week, n=3) in respect to EBV infected controls (n=2). RESULTS: EBV-fLuc was detectable one week after infection by non-invasive optical imaging in the spleen, from where it spread rapidly and systemically. Among the EBV-infected mice, 8/18 (=44%) developed macroscopically visible tumors in the spleen. For further analyses of the data, we then compared EBV-infected mice with ("EBV-Tumor") or without ("EBV") macroscopic tumors. At 6 weeks post-infection, the relative CD8+ T cell frequencies increased significantly and constantly (control Vs. EBV p=0.0021, control Vs. EBV-Tumor p=<0.0001, EBV Vs. EBV-Tumor p=0.0072). For absolute cell counts in tissues, CD8+ T cell increases were more dramatic in mice infected with EBV and developing tumors. These differences amounted to approximately tenfold relative to controls and 3-fold relative to mice not developing tumors. Mice infected with EBV showed 90-100% of the CD4+ and CD8+ T cells in lymphatic tissues expressing PD-1. Mice with EBV-tumors showed twice as many PD-1+ CD4+ and three times as many PD-1+ CD8+ T cells as infected mice without tumors. Histopathology combined with EBER in situ hybridization, showed foci of EBV infected cells in close association with PD-1+ infiltrating lymphocytes, often in perivascular regions. This model was then used to evaluate dose-dependent effects of pembrolizumab. The check-point inhibitor controlled EBV-fLUC spread for 2 weeks, but later prompted increased levels of infections. At endpoint analyses, mice receiving pembrolizumab showed larger dissemination of tumors. CONCLUSIONS: We are currently performing additional experiments in order to elucidate this mechanism of EBV rebound. This humanized mouse model contributes to risk assessment prior to clinical trials of the use of checkpoint inhibitors in patients after transplantations at high risk of EBV infections. Disclosures Ganser: Novartis: Membership on an entity's Board of Directors or advisory committees.

scholarly journals EBV-associated mononucleosis does not induce long-term global deficit in T-cell responsiveness to IL-15

Blood ◽  
2009 ◽  
Vol 113 (19) ◽  
pp. 4541-4547 ◽  
Author(s):  
Julien Giron-Michel ◽  
Fanny Menard ◽  
Simone Negrini ◽  
Aurore Devocelle ◽  
Bruno Azzarone ◽  
...  
Keyword(s):  
T Cell ◽  
Epstein Barr Virus ◽  
Epstein Barr Virus Infection ◽  
Barr Virus ◽  
Immune Balance ◽  
Disease Episode ◽  
Interleukin 15 ◽  
Epstein Barr ◽  
Barr Virus Infection

Abstract It has been reported that infectious mononucleosis (IM)–symptomatic primary Epstein-Barr virus infection produces a global down-regulation of interleukin-15 receptor-α (IL-15Rα) on T cells and natural killer cells associated with a defective IL-15 responsiveness that lasts for many years after the disease episode. In contrast with these results, our data indicate that, in the T-cell compartment derived from remote IM subjects, there is no quantitative or qualitative defect in the expression of the IL-15Rα chain and no deficit in T-cell responsiveness to IL-15. We observed efficient signal transduction, survival, and proliferation even in response to low IL-15 concentrations. These data are relevant and shed new light on the immune long-term response in IM subjects because they contradict the hypothesis that defects in Epstein-Barr virus–host immune balance may be correlated with a long-lasting global deficit in T-cell responsiveness to IL-15.

scholarly journals Skewed T cell responses to Epstein-Barr virus in long-term asymptomatic kidney transplant recipients

PLoS ONE ◽  
2019 ◽  
Vol 14 (10) ◽  
pp. e0224211
Author(s):  
Cecilia Nakid-Cordero ◽  
Nadia Arzouk ◽  
Nicolas Gauthier ◽  
Nadine Tarantino ◽  
Martin Larsen ◽  
...  
Keyword(s):  
T Cell ◽  
Kidney Transplant ◽  
Epstein Barr Virus ◽  
T Cell Responses ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Barr Virus ◽  
Cell Responses ◽  
Epstein Barr
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