Epstein-Barr virus induces the differentiation of semi-mature dendritic cells from cord blood monocytes

详细信息    查看全文

• 作者：Ying-Ying Jin^a ; ¹ ; Xi Wang^b ; ¹ ; Jing Du^b ; Rui-Ming Cao^b ; Helen K.W. Law^c ; Juan-Juan Wang^b ; Tong-Xin Chen^a ; ^d ; ^{tongxinc@yahoo.com" class="auth_mail}
• 刊名：Human Immunology
• 出版年：April, 2014
• 年：2014
• 卷：75
• 期：4
• 页码：306-316
• 全文大小：872 K

文摘

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 鈥渟emi-mature鈥?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 鈥減athogen-driven regulatory mature DCs鈥?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.

Conclusion

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.