EBV promotes human CD8 NKT cell development

• Published in: PLoS pathogens 2010-05, Vol.6 (5), p.e1000915
• Main Authors: He, Yuling, Xiao, Ruijing, Ji, Xiang, Li, Li, Chen, Lang, Xiong, Jie, Xiao, Wei, Wang, Yujuan, Zhang, Lijun, Zhou, Rui, Tan, Xinti, Bi, Yongyi, Jiang, Yan-Ping, Jin, Youxin, Tan, Jinquan
• Format: Article
• Language: English
• Subjects: Animals; Antigens; CD8-Positive T-Lymphocytes - cytology; CD8-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - virology; Cell Differentiation - immunology; Cell Lineage - immunology; Cells, Cultured; Chimera; Developmental Biology/Cell Differentiation; Epstein-Barr virus; Epstein-Barr Virus Infections - immunology; Experiments; Female; Flow Cytometry; Gene Expression - immunology; Hodgkin Disease - immunology; Humans; Immunology; Immunology/Immunity to Infections; Immunology/Innate Immunity; Immunology/Leukocyte Development; Infectious Mononucleosis - immunology; Interferon-gamma - metabolism; Interleukin-7 - genetics; Killer Cells, Natural - cytology; Killer Cells, Natural - immunology; Killer Cells, Natural - virology; Lymphoma; Mice; Mice, SCID; Organ Culture Techniques; Perforin; Pore Forming Cytotoxic Proteins - metabolism; R&D; Research & development; T cell receptors; Technological change; Thymus Gland - immunology; Thymus Gland - virology; Viral infections
• ISSN: 1553-7374; 1553-7366; 1553-7374
• DOI: 10.1371/journal.ppat.1000915

The reports on the origin of human CD8(+) Valpha24(+) T-cell receptor (TCR) natural killer T (NKT) cells are controversial. The underlying mechanism that controls human CD4 versus CD8 NKT cell development is not well-characterized. In the present study, we have studied total 177 eligible patients and subjects including 128 healthy latent Epstein-Barr-virus(EBV)-infected subjects, 17 newly-onset acute infectious mononucleosis patients, 16 newly-diagnosed EBV-associated Hodgkin lymphoma patients, and 16 EBV-negative normal control subjects. We have established human-thymus/liver-SCID chimera, reaggregated thymic organ culture, and fetal thymic organ culture. We here show that the average frequency of total and CD8(+) NKT cells in PBMCs from 128 healthy latent EBV-infected subjects is significantly higher than in 17 acute EBV infectious mononucleosis patients, 16 EBV-associated Hodgkin lymphoma patients, and 16 EBV-negative normal control subjects. However, the frequency of total and CD8(+) NKT cells is remarkably increased in the acute EBV infectious mononucleosis patients at year 1 post-onset. EBV-challenge promotes CD8(+) NKT cell development in the thymus of human-thymus/liver-SCID chimeras. The frequency of total (3% of thymic cells) and CD8(+) NKT cells ( approximately 25% of NKT cells) is significantly increased in EBV-challenged chimeras, compared to those in the unchallenged chimeras (