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Blood, 15 September 2006, Vol. 108, No. 6, pp. 1957-1964.
Prepublished online as a Blood First Edition Paper on May 16, 2006; DOI 10.1182/blood-2006-03-010918.
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IMMUNOBIOLOGY
Opposing roles of blood myeloid and plasmacytoid dendritic cells in HIV-1 infection of T cells: transmission facilitation versus replication inhibition
Fedde Groot,
Toni M. M. van Capel,
Martien L. Kapsenberg,
Ben Berkhout, and
Esther C. de Jong
From the Department of Human Retrovirology, the Department of Cell Biology and Histology, and the Department of Dermatology, Academic Medical Center, University of Amsterdam, The Netherlands.
CD11c+ myeloid dendritic cells (MDCs) and CD11c– CD123+ plasmacytoid DCs (PDCs) have been identified as main human DC subsets. MDCs are professional antigen-presenting cells for T cells, and include Langerhans cells, dermal DCs, and interstitial DCs. They have been associated with HIV-1 capture and sexual transmission, whereas PDCs play an important role in the innate immune responses to different types of viruses, including HIV-1. To compare the influence of MDCs and PDCs on HIV-1 infection of T cells, we isolated donor-matched MDCs and PDCs from peripheral blood, activated them by adding different maturation-inducing compounds, and cocultured them with T cells and HIV-1. We found that MDCs enhance HIV-1 infection through capture of the virus and subsequent transmission to T cells, and that differently matured MDC subsets have different HIV-1 transmission efficiencies. These differences were not due to soluble factors, viral capture differences, or the expression of integrins ICAM-1, -2, -3, or LFA-1. In contrast, regardless of their state of maturation, PDCs inhibit HIV-1 replication in T cells through the secretion of IFN and an additional, unidentified small molecule. This study shows that the 2 main types of DCs have opposing roles in HIV-1 infection of T cells.
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