scholarly journals Epstein-Barr virus, B cell lymphoproliferative disease, and SCID mice: Modeling T cell immunotherapy in vivo

2011 ◽  
Vol 83 (9) ◽  
pp. 1585-1596 ◽  
Author(s):  
I. Johannessen ◽  
L. Bieleski ◽  
G. Urquhart ◽  
S.L. Watson ◽  
P. Wingate ◽  
...  
Keyword(s):  
T Cell ◽  
B Cell ◽  
Epstein Barr Virus ◽  
Lymphoproliferative Disease ◽  
Scid Mice ◽  
Barr Virus ◽  
Cell Immunotherapy ◽  
Epstein Barr ◽  
T Cell Immunotherapy

scholarly journals Human Epstein-Barr virus (EBV)-specific cytotoxic T lymphocytes home preferentially to and induce selective regressions of autologous EBV-induced B cell lymphoproliferations in xenografted C.B-17 scid/scid mice.

1996 ◽  
Vol 183 (3) ◽  
pp. 1215-1228 ◽  
Author(s):  
J F Lacerda ◽  
M Ladanyi ◽  
D C Louie ◽  
J M Fernandez ◽  
E B Papadopoulos ◽  
...  
Keyword(s):  
T Cells ◽  
B Cell ◽  
Epstein Barr Virus ◽  
Scid Mice ◽  
Barr Virus ◽  
Target Ratio ◽  
Epstein Barr ◽  
Effector Target

C.B-17 scid/scid (severe combined immunodeficiency [SCID]) mice inoculated with peripheral blood lymphocytes from Epstein-Barr virus (EBV)-seropositive donors, or with EBV-transformed lymphoblastoid B cell lines (EBV-LCL), develop lethal human EBV+ B cell lymphoproliferative disorders (EBV-LPD) with characteristics similar to those arising in immunodeficient patients. Using this model, we examined the capacity of human effector cells to control human EBV-LPD. SCID mice received rabbit anti-asialo GM1 antiserum to abrogate endogenous natural killer-cell function. Preliminary experiments showed that adoptive transfer of peripheral blood mononuclear cells (PBMC), purified T cells, interleukin (IL) 2-activated PBMC or anti-CD3-activated T cells derived from EBV-seropositive donors did not result in improved survival of treated mice (in vivo effector/target ratio 2:1 to 1:1). In contrast, EBV-specific cytotoxic T lymphocytes (CTL), derived from EBV-seropositive donors and expanded in vitro, exhibited strong EBV-specific and HLA-restricted activity both in vitro and in vivo. SCID mice inoculated intraperitoneally with autologous but not with HLA-mismatched EBV-LCL had significantly improved survival relative to untreated mice after inoculation of EBV-specific CTL either intraperitoneally (P<0.001) or intravenously (P<0.001) (in vivo effector/target ratio 1:1). SCID mice bearing large subcutaneous EBV+ tumors and treated intravenously with 10(7) EBV-specific CTL achieved complete tumor regression. Both CTL- and CTL-plus-IL-2-treated mice survived significantly longer than untreated animals or animals treated with IL-2 alone (P = 0.0004 and P<0.02, respectively). SCID mice bearing two subcutaneous EBV+ tumors, one autologous and the other HLA mismatched to the EBV-specific CTL donor, had regression of only the autologous tumor after intravenous infusion of 10(7) EBV-specific CTL. Moreover, we could demonstrate preferential homing of PKH26-labeled EBV-specific CTL to autologous but not to HLA-mismatched EBV+ tumors as early as 24 h after intravenous adoptive transfer. Immunophenotypic analyses also demonstrated preferential infiltration of T cells into the autologous EBV+ tumor in SCID mice bearing both the autologous and either fully HLA-mismatched or genotypically related haplotype-sharing EBV+ tumors. The human T cells infiltrating EBV+ tumors were CD3+ and, predominantly, CD8+CD4-. Our results indicate that EBV-specific CTL preferentially localize to and infiltrate EBV+ tumors bearing the appropriate HLA antigens and thereafter induce targeted regressions of disease.

Treatment of Epstein-Barr-virus-associated primary CNS B cell lymphoma with allogeneic T-cell immunotherapy and stem-cell transplantation

2005 ◽  
Vol 6 (5) ◽  
pp. 344-346 ◽  
Author(s):  
Robert F Wynn ◽  
Peter D Arkwright ◽  
Tanzina Haque ◽  
Maged I Gharib ◽  
Gwen Wilkie ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
B Cell ◽  
Epstein Barr Virus ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Barr Virus ◽  
Cell Immunotherapy ◽  
Epstein Barr ◽  
T Cell Immunotherapy

scholarly journals Impaired Epstein-Barr virus–specific CD8+ T-cell function in X-linked lymphoproliferative disease is restricted to SLAM family–positive B-cell targets

Blood ◽  
2010 ◽  
Vol 116 (17) ◽  
pp. 3249-3257 ◽  
Author(s):  
Andrew D. Hislop ◽  
Umaimainthan Palendira ◽  
Alison M. Leese ◽  
Peter D. Arkwright ◽  
Pierre S. Rohrlich ◽  
...  
Keyword(s):  
T Cell ◽  
B Cell ◽  
Epstein Barr Virus ◽  
Cd8 T Cell ◽  
Lymphoproliferative Disease ◽  
Target Cells ◽  
Barr Virus ◽  
Ebv Infection ◽  
Slam Family ◽  
Epstein Barr

Abstract X-linked lymphoproliferative disease (XLP) is a condition associated with mutations in the signaling lymphocytic activation molecule (SLAM)–associated protein (SAP; SH2D1A). SAP functions as an adaptor, binding to and recruiting signaling molecules to SLAM family receptors expressed on T and natural killer cells. XLP is associated with extreme sensitivity to primary Epstein-Barr virus (EBV) infection, often leading to a lethal infectious mononucleosis. To investigate EBV-specific immunity in XLP patients, we studied 5 individuals who had survived EBV infection and found CD8+ T-cell responses numerically comparable with healthy donors. However, further investigation of in vitro–derived CD8+ T-cell clones established from 2 of these donors showed they efficiently recognized SLAM ligand–negative target cells expressing EBV antigens, but showed impaired recognition of EBV-transformed, SLAM ligand–positive, lymphoblastoid cell lines (LCLs). Importantly, LCL recognition was restored when interactions between the SLAM receptors CD244 and natural killer–, T-, and B-cell antigen (NTBA) and their ligands on LCLs were blocked. We propose that XLP patients' particular sensitivity to EBV, and not to other viruses, reflects at least in part EBV's strict tropism for B lymphocytes and the often inability of the CD8+ T-cell response to contain the primary infection of SLAM ligand–expressing target cells.

scholarly journals Systemic T-Cell Lymphoproliferative Disease Associated with Epstein-Barr Virus: A Literature Review and a Case Report

2021 ◽  
Vol 14 (4) ◽  
pp. 477-487
Author(s):  
E.A. Shalamova ◽  
Alla Mikhailovna Kovrigina ◽  
I.A. Shupletsova ◽  
E.E. Nikulina ◽  
V.D. Latyshev ◽  
...  
Keyword(s):  
T Cell ◽  
B Cell ◽  
Epstein Barr Virus ◽  
Complex Analysis ◽  
Laboratory Data ◽  
Lymphoproliferative Disease ◽  
Lymphoproliferative Diseases ◽  
Barr Virus ◽  
North East ◽  
Epstein Barr

Epstein-Barr virus (EBV) is ubiquitous, being identified in 90-95 % of adults. Its reactivation in immunodeficiency conditions often leads to clonal transformation of B-lymphocytes and development of B-cell lymphoproliferative diseases (LPD) and B-cell lymphomas. At the same time, in the countries of North-East and East Asia, as well as Latin America, non-immunocompromised patients sometimes demonstrate the development of EBV-associated T-cell lymphoproliferative diseases. The present paper reports a rare case of EBV-associated systemic T-LPD with lymphadenopathy, splenomegaly as well as acute autoimmune hemolytic anemia in a man of Caucasian race. Complex analysis of anamnestic, pathomorphological, and laboratory data allowed to distinguish this disease from T-cell lymphoma and choose the appropriate patient management strategy.

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