scholarly journals Epstein–Barr virus-specific adoptive immunotherapy for progressive multiple sclerosis

2014 ◽  
Vol 20 (11) ◽  
pp. 1541-1544 ◽  
Author(s):  
Michael P Pender ◽  
Peter A Csurhes ◽  
Corey Smith ◽  
Leone Beagley ◽  
Kaye D Hooper ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
T Cells ◽  
Adoptive Immunotherapy ◽  
Epstein Barr Virus ◽  
Progressive Multiple Sclerosis ◽  
Resonance Imaging ◽  
Barr Virus ◽  
The Central Nervous System ◽  
Epstein Barr

Defective control of Epstein–Barr virus (EBV) infection by cytotoxic CD8+ T cells might predispose to multiple sclerosis (MS) by allowing EBV-infected autoreactive B cells to accumulate in the central nervous system. We have treated a patient with secondary progressive MS with in vitro-expanded autologous EBV-specific CD8+ T cells directed against viral latent proteins. This adoptive immunotherapy had no adverse effects and the patient showed clinical improvement with reduced disease activity on magnetic resonance imaging and decreased intrathecal immunoglobulin production. This is the first report of the use of EBV-specific adoptive immunotherapy to treat MS or any other autoimmune disease.

scholarly journals Deficiency of CD8+ effector memory T cells is an early and persistent feature of multiple sclerosis

2014 ◽  
Vol 20 (14) ◽  
pp. 1825-1832 ◽  
Author(s):  
Michael P Pender ◽  
Peter A Csurhes ◽  
Casey MM Pfluger ◽  
Scott R Burrows
Keyword(s):  
Multiple Sclerosis ◽  
T Cells ◽  
T Cell ◽  
Epstein Barr Virus ◽  
Clinical Course ◽  
Effector Memory ◽  
Barr Virus ◽  
Effector Memory T Cells ◽  
The Central Nervous System ◽  
Epstein Barr

Background: Patients with multiple sclerosis (MS) have a deficiency of circulating CD8+ T cells, which might impair control of Epstein–Barr virus (EBV) and predispose to MS by allowing EBV-infected autoreactive B cells to accumulate in the central nervous system. Based on the expression of CD45RA and CD62L, CD4+ T cells and CD8+ T cells can be subdivided into four subsets with distinct homing and functional properties, namely: naïve, central memory, effector memory (EM) and effector memory re-expressing CD45RA (EMRA) cells. Objective: Our aim was to determine which memory subsets are involved in the CD8+ T cell deficiency and how these relate to clinical course. Methods: We used flow cytometry to analyze the memory phenotypes of T cells in the blood of 118 MS patients and 112 healthy subjects. Results: MS patients had a decreased frequency of EM (CD45RA–CD62L–) and EMRA (CD45RA+CD62L–) CD8+ T cells, which was present at the onset of disease and persisted throughout the clinical course. The frequencies of CD4+ EM and EMRA T cells were normal. Conclusion: Deficiency of effector memory CD8+ T cells is an early and persistent feature of MS and might underlie the impaired CD8+ T cell control of EBV.

Cytokine mRNA profile of Epstein–Barr virus-stimulated highly differentiated T cells in multiple sclerosis: A pilot study

2010 ◽  
Vol 225 (1-2) ◽  
pp. 167-170 ◽  
Author(s):  
Emilie Jaquiéry ◽  
Samantha Jilek ◽  
Myriam Schluep ◽  
Géraldine Le Goff ◽  
Miguel Garcia ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
T Cells ◽  
Pilot Study ◽  
Epstein Barr Virus ◽  
Cytokine Mrna ◽  
Barr Virus ◽  
Mrna Profile ◽  
Epstein Barr

scholarly journals Programmed death 1 is highly expressed on CD8+CD57+T cells in patients with stable multiple sclerosis and inhibits their cytotoxic response to Epstein-Barr virus

Immunology ◽  
2017 ◽  
Vol 152 (4) ◽  
pp. 660-676 ◽  
Author(s):  
Maria T. Cencioni ◽  
Roberta Magliozzi ◽  
Richard Nicholas ◽  
Rehiana Ali ◽  
Omar Malik ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
T Cells ◽  
Epstein Barr Virus ◽  
Barr Virus ◽  
Cytotoxic Response ◽  
Programmed Death ◽  
Programmed Death 1 ◽  
Epstein Barr

scholarly journals Analysis of the defects responsible for the impaired regulation of Epstein-Barr virus-induced B cell proliferation by rheumatoid arthritis lymphocytes. I. Diminished gamma interferon production in response to autologous stimulation.

1983 ◽  
Vol 157 (1) ◽  
pp. 173-188 ◽  
Author(s):  
F Hasler ◽  
H G Bluestein ◽  
N J Zvaifler ◽  
L B Epstein
Keyword(s):  
Cell Proliferation ◽  
T Cells ◽  
T Cell ◽  
B Cell ◽  
Epstein Barr Virus ◽  
Gamma Interferon ◽  
Barr Virus ◽  
T Cell Regulation ◽  
Epstein Barr

T cells of patients with rheumatoid arthritis (RA) do not control the rate of B lymphoblast transformation induced by Epstein-Barr virus (EBV) as efficiently as T cells from healthy individuals; thus, lymphoblast cell lines are established more readily in RA lymphocytes in vitro after EBV infection. In the present experiments, we have asked whether this T cell regulation can be reproduced by lymphocytes. We found that normal T cells, activated in allogeneic or autologous mixed leukocyte reactions (MLR), produce lymphokines that inhibit in vitro EBV-induced B cell proliferation. Allogeneic MLR supernatants inhibited EBV-induced DNA synthesis 62 +/- 4% (mean +/- SE) at 10 d post-infection, whereas autologous MLR supernatants suppressed it 50 +/- 3%. RA T cell supernatants produced in an allogeneic MLR suppressed as well as normal T cell supernatants (64 +/- 5% inhibition). In contrast, supernatants from RA autologous MLR had little inhibitory activity. EBV-induced DNA synthesis at 10 d was reduced only 8 +/- 3%, compared with the 50 +/- 3% suppressive activity of normal autologous MLR supernatants. The magnitude of the proliferative responses in the autologous MLR regenerating the lymphokines was similar in the normal and RA populations. After depletion of adherent cells from the RA auto-MLR stimulators, supernatant inhibitory activities increased to normal levels (from 11 +/- 6 [SE] to 52 +/- 6% [SE]). The inhibitory factor involved in the regulation of in vitro EBV infection is a protein with a molecular weight of approximately 50,000. Its activity is eliminated by hearing at 56 degrees C and by exposure to acid at pH 2. The inhibitory activity is blocked by mixing the MLR supernatants with a polyvalent antisera or monoclonal antibodies specific for human gamma interferon. Gamma interferon produced by activating T cells in allo- or auto-MLR can reproduce T cell-mediated regulation of EBV-induced B cell proliferation, and the failure of RA auto-MLR to generate that lymphokine parallels the defective T cell regulation of EBV-induced B cell proliferation characteristic of RA lymphoid cells.

scholarly journals The Outcomes of Epstein-Barr Virus Specific T Cells from Different Sources for EBV Infections in Recipients of Allogeneic Stem Cell Transplantation

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 3330-3330
Author(s):  
Ren Lin ◽  
Fen Huang ◽  
Zhiping Fan ◽  
Xiaoyan Shao ◽  
Guoxian Dai ◽  
...  
Keyword(s):  
T Cells ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Natural Science ◽  
Epstein Barr Virus ◽  
Third Party ◽  
Barr Virus ◽  
Ifn Γ ◽  
Epstein Barr

Abstract Background Epstein-Barr virus (EBV) specific T cells have been proven effective in prevention and treatment of EBV associated-diseases after allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, the optimal source of EBV specific T cells remains unclear. Here, we compared autologous and donor derived EBV specific T cells with respect to generation ex vivo and the efficacy on EBV infections in the recipients of allo-HSCT. Methods Thirty-eight patients with EBV infections were enrolled in this study, including 21 with EBV-emia and 17 with EBV associated post-transplant lymphoproliferative disease (PTLD). EBV specific T cells were generated by immunomagnetic isolation from all the recipients themselves and second-party (original HSCT donor, n=25) or third-party related donors (n=25). The donors were EBV seropositive. The percentages of IFN-γ+ EBV specific T cells in the products and cytotoxic capacity of EBV specific T cells were evaluated. Results The median time of EBV infections was 49 days (range, 24-1479 days) post-transplants. The generation of autologous EBV specific T cells failed within 14 days of culture in all the patients because the numbers of cells were insufficient for treatment. Donor derived EBV specific T cells were expanded in vitro for 14 days until the sufficient number (≥ 109) was generated. The percentages of IFN-γ+ EBV specific T cells were comparable in the products generated from second- and third-party donors, but both higher than autologous derived EBV specific T cells. Cytotoxic capacity of EBV specific T cells was lower in autologous EBV specific T cells than donor derived EBV specific T cells. Twenty-one patients with refractory EBV infections (12 with EBV-emia and 9 with PTLD) received EBV specific T cells treatment, including 13 receiving second-party and 8 third-party EBV specific T cells. After treatments, 20 patients exhibited EBV clearance in blood within 6 weeks without recurrence and 1 with PTLD died at 3 weeks after the first infusion of EBV specific T cells with the decline of EBV-DNA copies. Other 8 patients with PTLD received complete remission after treatment. The response rates were not different between the patients receiving second- and third-party donor derived EBV specific T cells. One of the 13 patients with second-party derived EBV specific T cells developed pre-existing chronic graft-versus-host disease (GVHD) exacerbation while 1 developed grade Ⅱ aGVHD in the 8 patients receiving third-party donor derived EBV specific T cells. Conclusion The efficacy of EBV-specific T cells derived from second- and third-party are comparable in treatment of EBV infections after allo-HSCT. Autologous derived EBV-specific T cells seems not suitable for treatment because of poor production in vitro. Disclosures Fan: National Natural Science Foundation of China (No. 81600141, No. 81770190) and Natural Science Foundation of Guangdong Province (No. 2016A030310390): Research Funding.

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