HIV-1 infection of placental cord blood monocyte-derived dendritic cells

• Published in: Journal of hematotherapy & stem cell research Vol. 10; no. 5; p. 609
• Main Authors: Folcik, R M, Merrill, J D, Li, Y, Guo, C J, Douglas, S D, Starr, S E, Ho, W Z
• Format: Journal Article
• Language: English
• Published: United States 01.10.2001
• Subjects: Antigens, CD; Antigens, CD34 - immunology; CD4 Antigens - genetics; CD83 Antigen; Cell Differentiation - drug effects; Cell Differentiation - immunology; Cell Line; Cells, Cultured; Dendritic Cells - drug effects; Dendritic Cells - metabolism; Dendritic Cells - virology; Female; Fetal Blood - cytology; Fetal Blood - drug effects; Fetal Blood - immunology; Gene Expression Regulation - drug effects; Granulocyte-Macrophage Colony-Stimulating Factor - pharmacology; HIV Infections - metabolism; HIV Infections - virology; HIV-1 - genetics; Humans; Immunoglobulins - immunology; Interleukin-4 - pharmacology; Lipopolysaccharide Receptors - immunology; Luciferases - genetics; Luciferases - metabolism; Macrophages - drug effects; Macrophages - immunology; Macrophages - metabolism; Membrane Glycoproteins - immunology; Monocytes - cytology; Monocytes - drug effects; Monocytes - immunology; Placenta; Pregnancy; Receptors, CCR5 - genetics; Recombinant Fusion Proteins - genetics; Recombinant Fusion Proteins - metabolism; RNA, Messenger - drug effects; RNA, Messenger - genetics; RNA, Messenger - metabolism; Time Factors; Tumor Necrosis Factor-alpha - pharmacology
• ISSN: 1525-8165
• DOI: 10.1089/152581601753193823

Dendritic cells (DC), the most potent antigen-presenting cells (APC), have been implicated as the initial targets of HIV infection in skin and mucosal surfaces. DC can be generated in vitro from blood-isolated CD14(+) monocytes or CD34(+) hematopoietic progenitor cells in the presence of various cytokines. In this study, we investigated whether monocytes obtained from placental cord blood are capable of differentiation into dendritic cells when cultured with a combination of cytokines - granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-4 (IL-4), and tumor necrosis factor-alpha (TNF-alpha). We then examined HIV infection, HIV receptor (CD4, CCR5) expression, and beta-chemokine [macrophage inflammatory protein-1alpha and -1beta (MIP-1alpha, MIP-1beta)] production by placental cord monocyte-derived dendritic cells (MDDC) as compared to that of autologous cord monocyte-derived macrophages (MDM). Monocytes isolated from placental cord blood differentiate into DC after 7 days in culture with the mixture of cytokines, as demonstrated by development of characteristic DC morphology, loss of CD14 expression, and gain of CD83, a marker for mature DC. Mature cord MDDC had significantly lower susceptibility to M-tropic ADA (CCR5-dependent) envelope-pseudotyped HIV infection in comparison to autologous placental cord MDM, whereas there was no significant difference in virus replication in cord MDDC and MDM infected with murine leukemia virus envelope-pseudotyped HIV (HIV receptor-independent). This limited susceptibility of cord MDDC to M-tropic HIV infection may be due to lower expression of CD4 and CCR5 on the cell membrane and higher production of MIP-1alpha and MIP-1beta. These data provide important information toward our understanding of the biological properties of cord MDDC in relation to HIV infection.