EBV Promotes Human CD8(+) NKT Cell Development

	EBV Promotes Human CD8(+) NKT Cell Development
	He, YL; Xiao, RJ; Ji, X; Li, L; Chen, L; Xiong, J; Xiao, W; Wang, YJ; Zhang, LJ; Zhou, R
刊名	PLOS PATHOGENS
	2010
卷号	6 期号:5 页码:e1000915-e1000915
通讯作者	He, YL (reprint author), Wuhan Univ, Dept Immunol, Sch Med, Wuhan 430072, Peoples R China.,flying_bird2004@sina.com ; jinquan_tan@whu.edu.cn
英文摘要	The reports on the origin of human CD8(+) V alpha 24(+) 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 (similar to 25% of NKT cells) is significantly increased in EBV-challenged chimeras, compared to those in the unchallenged chimeras (<0.01% of thymic cells, CD8(+) NKT cells undetectable, respectively). The EBV-induced increase in thymic NKT cells is also reflected in the periphery, where there is an increase in total and CD8(+) NKT cells in liver and peripheral blood in EBV-challenged chimeras. EBV-induced thymic CD8(+) NKT cells display an activated memory phenotype (CD69(+)CD45RO(hi)CD161(+)CD62L(lo)). After EBV-challenge, a proportion of NKT precursors diverges from DP thymocytes, develops and differentiates into mature CD8(+) NKT cells in thymus in EBV-challenged human-thymus/liver-SCID chimeras or reaggregated thymic organ cultures. Thymic antigen-presenting EBV-infected dendritic cells are required for this process. IL-7, produced mainly by thymic dendritic cells, is a major and essential factor for CD8(+) NKT cell differentiation in EBV-challenged human-thymus/liver-SCID chimeras and fetal thymic organ cultures. Additionally, these EBV-induced CD8(+) NKT cells produce remarkably more perforin than that in counterpart CD4(+) NKT cells, and predominately express CD8 alpha alpha homodimer in their co-receptor. Thus, upon interaction with certain viruses, CD8 lineage-specific NKT cells are developed, differentiated and matured intrathymically, a finding with potential therapeutic importance against viral infections and tumors.
学科主题	Microbiology; Parasitology; Virology
类目[WOS]	Microbiology ; Parasitology ; Virology
关键词[WOS]	KILLER T-CELLS ; EPSTEIN-BARR-VIRUS ; NATURAL-KILLER ; ALPHA-GALACTOSYLCERAMIDE ; DENDRITIC CELLS ; HUMAN THYMOCYTES ; SELECTIVE LOSS ; INFECTION ; CD4(+) ; EXPANSION
收录类别	SCI
语种	英语
WOS记录号	WOS:000278759900034
内容类型	期刊论文
版本	出版稿
源URL	[http://202.127.25.143/handle/331003/1000]
专题	上海生化细胞研究所_上海生科院生化细胞研究所
推荐引用方式 GB/T 7714	He, YL,Xiao, RJ,Ji, X,et al. EBV Promotes Human CD8(+) NKT Cell Development[J]. PLOS PATHOGENS,2010,6(5):e1000915-e1000915.
APA	He, YL.,Xiao, RJ.,Ji, X.,Li, L.,Chen, L.,...&Tan, JQ.(2010).EBV Promotes Human CD8(+) NKT Cell Development.PLOS PATHOGENS,6(5),e1000915-e1000915.
MLA	He, YL,et al."EBV Promotes Human CD8(+) NKT Cell Development".PLOS PATHOGENS 6.5(2010):e1000915-e1000915.