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Leukemia & Lymphoma Volume 56, 2015 - Issue 4
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Original Article: Research

Increased T-cell responses to Epstein–Barr virus with high viral load in patients with Epstein–Barr virus-positive diffuse large B-cell lymphoma

Satoko MorishimaDepartment of Hematology, Fujita Health University School of Medicine, Toyoake, Japan;Division of Immunology, Aichi Cancer Center Research Institute, Nagoya, Japan;Department of Hematology and Cell Therapy, Aichi Cancer Center Hospital, Nagoya, JapanCorrespondence[email protected]
,
Shigeo NakamuraDepartment of Pathology and Clinical Laboratories, Nagoya University Hospital, Nagoya, Japan
,
Kazuhito YamamotoDepartment of Hematology and Cell Therapy, Aichi Cancer Center Hospital, Nagoya, Japan
,
Hidemasa MiyauchiHealth System, Inc., Jishokai Group, Nagoya, Japan
,
Yoshitoyo KagamiDepartment of Hematology and Cell Therapy, Aichi Cancer Center Hospital, Nagoya, Japan;Department of Hematology, Toyota Kosei Hospital, Toyota, Aichi, Japan
,
Tomohiro KinoshitaDepartment of Hematology and Cell Therapy, Aichi Cancer Center Hospital, Nagoya, Japan;Department of Hematology and Oncology, Nagoya University Graduate School of Medicine, Nagoya, Japan
,
Hiroshi OnodaDepartment of Hematology and Cell Therapy, Aichi Cancer Center Hospital, Nagoya, Japan
,
Yasushi YatabeDepartment of Clinical Pathology, Aichi Cancer Center Hospital, Nagoya, Japan
,
Masafumi ItoDepartment of Pathology, Japanese Red Cross Nagoya First Hospital, Nagoya, Japan
,
Kouichi MiyamuraDepartment of Hematology, Japanese Red Cross Nagoya First Hospital, Nagoya, Japan
,
Hirokazu NagaiClinical Research Center, National Hospital Organization Nagoya Medical Center, Nagoya, Japan
,
Suzuko MoritaniDepartment of Pathology, National Hospital Organization Nagoya Medical Center, Nagoya, Japan
,
Isamu SugiuraDepartment of Hematology, Toyohashi Municipal Hospital, Toyohashi, Japan
,
Keitaro TsushitaDepartment of Hematology, Social Insurance Chukyo Hospital, Nagoya, Japan
,
Hidetsugu MiharaDepartment of Internal Medicine, Division of Hematology, Aichi Medical University School of Medicine, Nagakute, Japan
,
Kaneyuki OhbayashiDepartment of Internal Medicine, Nishio Municipal Hospital, Nishio, Japan
,
Sachiko IbaDepartment of Hematology, Fujita Health University School of Medicine, Toyoake, Japan
,
Nobuhiko EmiDepartment of Hematology, Fujita Health University School of Medicine, Toyoake, Japan
,
Masataka OkamotoDepartment of Hematology, Fujita Health University School of Medicine, Toyoake, Japan
,
Seiko IwataDepartment of Virology, Nagoya University Graduate School of Medicine, Nagoya, Japan
,
Hiroshi KimuraDepartment of Virology, Nagoya University Graduate School of Medicine, Nagoya, Japan
,
Kiyotaka KuzushimaDivision of Immunology, Aichi Cancer Center Research Institute, Nagoya, Japan
&
Yasuo MorishimaDepartment of Hematology and Cell Therapy, Aichi Cancer Center Hospital, Nagoya, Japan;Division of Epidemiology and Prevention, Aichi Cancer Center Research Institute, Nagoya, Japan
 show all
Pages 1072-1078 | Received 23 Jan 2014, Accepted 19 Jun 2014, Published online: 13 Aug 2014
 
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Abstract

The immunological status of patients with Epstein–Barr virus-positive diffuse large B-cell lymphoma (EBV+ DLBCL) without obvious immunodeficiency has not been elucidated. A multicenter prospective study was conducted to assess pretreatment T-cell responses to EBV, EBV-DNA load and anti-EBV antibody in these patients. The proliferative and interferon (IFN)-γ-producing capacity of T-cells in response to autologous B-lymphoblastoid cell lines was determined using carboxyfluorescein diacetate succinimidyl ester (CFSE)-based assay. Frequencies of EBV-specific CD4+ T-cells in patients with EBV+ DLBCL (n = 13) were significantly higher than in healthy controls (HCs) (n = 16) after both ex vivo and in vitro stimulation. Frequencies of EBV-specific CD8+ T-cells in patients with EBV+ DLBCL tended to be higher than in HCs after in vitro stimulation. Patients with EBV+ DLBCL also showed increased immunoglobulin G (IgG) responses to lytic EBV-encoded antigens. Pretreatment plasma EBV-DNA level was significantly higher in patients with EBV+ DLBCL than in patients with EBV− DLBCL or HCs. In conclusion, EBV-specific T-cells showed increased reactivity, accompanied by higher levels of plasma virus DNA in patients with EBV+ DLBCL.

Acknowledgements

We thank all doctors of the participating hospitals who contributed data to this publication, and Ms. Mako Hagino for technical assistance. We are grateful for the support of the following agencies: Grant-in-Aid for Cancer Research from the Ministry of Health, Labor and Welfare of Japan (Clinical Cancer Research H22-029) and Fujita Health University (SaM).

Potential conflict of interest

Disclosure forms provided by the authors are available with the full text of this article at www.informahealthcare.com/lal.

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