title: Epstein-Barr virus induces the differentiation of semi-mature dendritic cells from cord blood monocytes.
abstract: BACKGROUND
  Epstein-Barr virus (EBV) is a tumorigenic virus which has effectively infected nearly all human beings with over 95% adult being seropositive. The persistence of latent EBV infection is not fully understood. Recent studies point towards a hypothesis of immune suppression and immune evasion involving regulatory T cells (Tregs) and dendritic cells (DCs). We sought to explore the mechanism of EBV suppression and immune evasion.
  
  
  METHODS
  We compared the effects of EBV on cord blood (CB) and adult DCs differentiation and maturation including phenotype by flow cytometry, cytokine by ELISA and RT-PCR. And we evaluated the function of DC by co-culture DC and Treg by detection the expression of Foxp3, the phenotype and the cytokine profile of Tregs by flow cytometry.
  
  
  RESULTS
  CB DCs derived from EBV-infected CB monocytes or from EBV-infected CB immature DCs (iDCs) displayed distinct phenotypes of "semi-mature" DCs with high expression of co-stimulatory molecules, such as CD40, CD80 and CD86 but low cytokine production, related to immune tolerance and homeostasis. While the EBV-infected adult iDCs resemble that of "pathogen-driven regulatory mature DCs" with high expression of co-stimulatory molecules, down-regulation of IL-12 secretion and up-regulation of IL-10 secretion, related to protection of host and immune evasion of pathogens. EBV infected cord blood monocytes-derived DCs drived Tregs development by driving the expression of Foxp3, increasing the expression of CTLA-4, decreasing the expression of GITR and promoted the generation of intracellular IL-2 and IL-10 by Tregs.
  
  
  CONCLUSIONS
  Epstein-Barr virus induces the differentiation of semi-mature dendritic cells from cord blood monocytes. The differences between CB and adult DCs suggested that the developmental maturity of the cells may affect their immune responses to EBV infection.
authors: Department of Allergy and Immunology, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China.
authors: Ying-Ying
authors: YY
authors: Jin
authors: Department of Pediatrics, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China.
authors: Xi
authors: X
authors: Wang
authors: Department of Pediatrics, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China.
authors: Jing
authors: J
authors: Du
authors: Department of Pediatrics, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China.
authors: Rui-Ming
authors: RM
authors: Cao
authors: Department of Pediatrics and Adolescent Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region.
authors: Helen K W
authors: HK
authors: Law
authors: Department of Pediatrics, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China.
authors: Juan-Juan
authors: JJ
authors: Wang
authors: Department of Allergy and Immunology, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China; Division of Immunology, Institute of Pediatric Translational Medicine, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China. Electronic address: tongxinc@yahoo.com.
authors: Tong-Xin
authors: TX
authors: Chen
mesh_terms: D000293:Adolescent; D000328:Adult; D002452:Cell Count; D002454:Cell Differentiation; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D020031:Epstein-Barr Virus Infections / Q000276:immunology* / Q000821:virology; D005312:Fetal Blood / Q000166:cytology; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000276:immunology*; D006801:Humans; D016130:Immunophenotyping; D007231:Infant, Newborn; D009000:Monocytes / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D010641:Phenotype; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism; D055815:Young Adult
chemical_list: D016207:Cytokines