Clonal origin of Epstein-Barr virus (EBV)-infected T/NK-cell subpopulations in EBV-positive T/NK-cell lymphoproliferative disorders of childhood

Shoichi Ohga, masataka ishimura, Goichi Yoshimoto, Toshihiro Miyamoto, Hidetoshi Takada, Tamami Tanaka, Koichi Ohshima, Yoshiyasu Ogawa, Ken Ichi Imadome, Yasunobu Abe, Koichi Akashi, Toshiro Hara

Research output: Contribution to journalArticle

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Abstract

Background: In Japan, chronic active Epstein-Barr virus infection (CAEBV) may manifest with infection of T-cells or NK-cells, clonal lymphoid proliferations, and overt lymphoid malignancy. These EBV-positive lymphoproliferative disorders (EBV +LPD) of childhood are related to, but distinct from the infectious mononucleosis-like CAEBV seen in Western populations. The clonal nature of viral infection within lymphoid subsets of patients with EBV +LPD of childhood is not well described. Objectives: Viral distribution and clonotype were assessed within T-cell subsets, NK-cells, and CD34 +stem cells following high purity cell sorting. Study design: Six Japanese patients with EBV +LPD of childhood (3 T-cell LPD and 3 NK-cell LPD) were recruited. Prior to immunochemotherapy, viral loads and clonal analyses of T-cell subsets, NK-cells, and CD34 +stem cells were studied by high-accuracy cell sorting (>99.5%), Southern blotting and real-time polymerase chain reaction. Results: Patient 1 had a monoclonal proliferation of EBV-infected γδT-cells and carried a lower copy number of EBV in αβT-cells. Patients 2 and 3 had clonal expansions of EBV-infected CD4 +T-cells, and lower EBV load in NK-cells. Patients 4, 5 and 6 had EBV +NK-cell expansions with higher EBV load than T-cells. EBV-terminal repeats were determined as clonal bands in the minor targeted populations of 5 patients. The size of terminal repeats indicated the same clonotype in minor subsets as in the major subsets of four patients. EBV was not, however, detected in the bone marrow-derived CD34 +stem cells of patients. Conclusions: A single EBV clonotype may infect multiple NK-cell and T-cell subsets of patients with EBV +LPD of childhood. CD34 +stem cells are spared, suggesting infection of more differentiated elements.

Original languageEnglish
Pages (from-to)31-37
Number of pages7
JournalJournal of Clinical Virology
Volume51
Issue number1
DOIs
Publication statusPublished - May 1 2011

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Lymphoproliferative Disorders
Human Herpesvirus 4
Natural Killer Cells
T-Lymphocytes
T-Lymphocyte Subsets
Stem Cells
Epstein-Barr Virus Infections
Terminal Repeat Sequences
Infectious Mononucleosis
Virus Diseases
Southern Blotting
Infection
Viral Load
Population
Real-Time Polymerase Chain Reaction
Japan

All Science Journal Classification (ASJC) codes

  • Infectious Diseases
  • Virology

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Clonal origin of Epstein-Barr virus (EBV)-infected T/NK-cell subpopulations in EBV-positive T/NK-cell lymphoproliferative disorders of childhood. / Ohga, Shoichi; ishimura, masataka; Yoshimoto, Goichi; Miyamoto, Toshihiro; Takada, Hidetoshi; Tanaka, Tamami; Ohshima, Koichi; Ogawa, Yoshiyasu; Imadome, Ken Ichi; Abe, Yasunobu; Akashi, Koichi; Hara, Toshiro.

In: Journal of Clinical Virology, Vol. 51, No. 1, 01.05.2011, p. 31-37.

Research output: Contribution to journalArticle

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abstract = "Background: In Japan, chronic active Epstein-Barr virus infection (CAEBV) may manifest with infection of T-cells or NK-cells, clonal lymphoid proliferations, and overt lymphoid malignancy. These EBV-positive lymphoproliferative disorders (EBV +LPD) of childhood are related to, but distinct from the infectious mononucleosis-like CAEBV seen in Western populations. The clonal nature of viral infection within lymphoid subsets of patients with EBV +LPD of childhood is not well described. Objectives: Viral distribution and clonotype were assessed within T-cell subsets, NK-cells, and CD34 +stem cells following high purity cell sorting. Study design: Six Japanese patients with EBV +LPD of childhood (3 T-cell LPD and 3 NK-cell LPD) were recruited. Prior to immunochemotherapy, viral loads and clonal analyses of T-cell subsets, NK-cells, and CD34 +stem cells were studied by high-accuracy cell sorting (>99.5{\%}), Southern blotting and real-time polymerase chain reaction. Results: Patient 1 had a monoclonal proliferation of EBV-infected γδT-cells and carried a lower copy number of EBV in αβT-cells. Patients 2 and 3 had clonal expansions of EBV-infected CD4 +T-cells, and lower EBV load in NK-cells. Patients 4, 5 and 6 had EBV +NK-cell expansions with higher EBV load than T-cells. EBV-terminal repeats were determined as clonal bands in the minor targeted populations of 5 patients. The size of terminal repeats indicated the same clonotype in minor subsets as in the major subsets of four patients. EBV was not, however, detected in the bone marrow-derived CD34 +stem cells of patients. Conclusions: A single EBV clonotype may infect multiple NK-cell and T-cell subsets of patients with EBV +LPD of childhood. CD34 +stem cells are spared, suggesting infection of more differentiated elements.",
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T1 - Clonal origin of Epstein-Barr virus (EBV)-infected T/NK-cell subpopulations in EBV-positive T/NK-cell lymphoproliferative disorders of childhood

AU - Ohga, Shoichi

AU - ishimura, masataka

AU - Yoshimoto, Goichi

AU - Miyamoto, Toshihiro

AU - Takada, Hidetoshi

AU - Tanaka, Tamami

AU - Ohshima, Koichi

AU - Ogawa, Yoshiyasu

AU - Imadome, Ken Ichi

AU - Abe, Yasunobu

AU - Akashi, Koichi

AU - Hara, Toshiro

PY - 2011/5/1

Y1 - 2011/5/1

N2 - Background: In Japan, chronic active Epstein-Barr virus infection (CAEBV) may manifest with infection of T-cells or NK-cells, clonal lymphoid proliferations, and overt lymphoid malignancy. These EBV-positive lymphoproliferative disorders (EBV +LPD) of childhood are related to, but distinct from the infectious mononucleosis-like CAEBV seen in Western populations. The clonal nature of viral infection within lymphoid subsets of patients with EBV +LPD of childhood is not well described. Objectives: Viral distribution and clonotype were assessed within T-cell subsets, NK-cells, and CD34 +stem cells following high purity cell sorting. Study design: Six Japanese patients with EBV +LPD of childhood (3 T-cell LPD and 3 NK-cell LPD) were recruited. Prior to immunochemotherapy, viral loads and clonal analyses of T-cell subsets, NK-cells, and CD34 +stem cells were studied by high-accuracy cell sorting (>99.5%), Southern blotting and real-time polymerase chain reaction. Results: Patient 1 had a monoclonal proliferation of EBV-infected γδT-cells and carried a lower copy number of EBV in αβT-cells. Patients 2 and 3 had clonal expansions of EBV-infected CD4 +T-cells, and lower EBV load in NK-cells. Patients 4, 5 and 6 had EBV +NK-cell expansions with higher EBV load than T-cells. EBV-terminal repeats were determined as clonal bands in the minor targeted populations of 5 patients. The size of terminal repeats indicated the same clonotype in minor subsets as in the major subsets of four patients. EBV was not, however, detected in the bone marrow-derived CD34 +stem cells of patients. Conclusions: A single EBV clonotype may infect multiple NK-cell and T-cell subsets of patients with EBV +LPD of childhood. CD34 +stem cells are spared, suggesting infection of more differentiated elements.

AB - Background: In Japan, chronic active Epstein-Barr virus infection (CAEBV) may manifest with infection of T-cells or NK-cells, clonal lymphoid proliferations, and overt lymphoid malignancy. These EBV-positive lymphoproliferative disorders (EBV +LPD) of childhood are related to, but distinct from the infectious mononucleosis-like CAEBV seen in Western populations. The clonal nature of viral infection within lymphoid subsets of patients with EBV +LPD of childhood is not well described. Objectives: Viral distribution and clonotype were assessed within T-cell subsets, NK-cells, and CD34 +stem cells following high purity cell sorting. Study design: Six Japanese patients with EBV +LPD of childhood (3 T-cell LPD and 3 NK-cell LPD) were recruited. Prior to immunochemotherapy, viral loads and clonal analyses of T-cell subsets, NK-cells, and CD34 +stem cells were studied by high-accuracy cell sorting (>99.5%), Southern blotting and real-time polymerase chain reaction. Results: Patient 1 had a monoclonal proliferation of EBV-infected γδT-cells and carried a lower copy number of EBV in αβT-cells. Patients 2 and 3 had clonal expansions of EBV-infected CD4 +T-cells, and lower EBV load in NK-cells. Patients 4, 5 and 6 had EBV +NK-cell expansions with higher EBV load than T-cells. EBV-terminal repeats were determined as clonal bands in the minor targeted populations of 5 patients. The size of terminal repeats indicated the same clonotype in minor subsets as in the major subsets of four patients. EBV was not, however, detected in the bone marrow-derived CD34 +stem cells of patients. Conclusions: A single EBV clonotype may infect multiple NK-cell and T-cell subsets of patients with EBV +LPD of childhood. CD34 +stem cells are spared, suggesting infection of more differentiated elements.

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