Download or read book The Role of DC-Sign in the Regulation of the Function and Survival of Dendritic Cells in HIV-1 Infection written by and published by . This book was released on 2005 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: (Uncorrected OCR) Abstract of thesis entitled The role of DC-SIGN in the regulation of the function and survival of dendritic cells in HIV-1 infection Submitted by Chung Pui Yee for the degree of Doctor of Philosophy at the University of Hong Kong in August 2004 Dendritic cells (DCs) are professional antigen-presenting cells that are pivotal in eliciting an efficient immune response against invading pathogens. DCs sample antigens from the periphery and subsequently migrate to lymphoid tissues, where they present processed antigen to T cells, mounting immune response. In addition to induction of primary T cell response, DCs are important in HIV-1 pathogenesis and serve as |rojan horses|to disseminate HIV-1 to the CD4+ permissive T cells. Dendritic Cell-Specific ICAM-3 Grabbing Nonintegrin (DC-SIGN) is a newly identified type II integral C-type lectin membrane protein and can bind HIV-1 viral envelope protein gp120. HIV-bound DCs migrate from peripheral sites to central lymphoid tissues and deliver virions in an infectious state to T cells, resulting in explosive viral replication. However, functional consequences of HIV-bound DCs through DC-SIGN are still unknown. Furthermore, the role of DC-SIGN in mediating the signal from DCs to T cells in HIV-1 infection is also poorly understood. Using monocyte-derived DCs, it is shown that binding of HIV-1 gp120 on DC-SIGN induced maturation of immature DCs as illustrated by the up-regulation of the surface expression of the costimulatory molecules as well as the downregulation of CCR5 by flow cytometry. DCs treated with either recombinant gp120, sera from HIV-1 infected individuals or in vitro propagated HIV-1 underwent apoptosis after cocultured with CD40 ligand transfectants for 3 days. Apoptosis was partially prevented by pretreatment of DCs with anti-DC-SIGN antibodies (DC28 and clone 120612). Activation of recombinant gp120-treated DCs through CD40 ligation resulted in a decreased capacity of IL-12 production. Similarly,