Preferential Entry and Productive Infection of CD4 Expressing Lymphoid Dendritic Cells by Macrophage-Tropic HIV-1

Abstract

Although cells of the dendritic cell [DC] lineage have been found in most tissues, only Langerhans cells and blood DCs have been examined for HIV-1 infection in vivo and in vitro. Reported levels of infection of blood DCs in vivo have ranged from high level infection with up to 20% of DCs infected¹ to virtually undetectable in patients at similar stages of the disease^2,3. A wide range of infectibility has also been found for blood DCs in vitro [see Cameron et al⁴ for review]. The differences may be at least partially attributed to the different isolation methods used and resultant phenotypic differences in the DC populations studied. Some studies have used DC-enriched populations mat contain only 30–75% DCs. In our hands, isolation methods that do not include specific depletion and cell sorting produce populations with unacceptable contamination with other cells including T cells. Dendritic cells are potent APCs and contamination with small numbers of T cells may assume a much greater significance than with less efficient APCs. DCs may induce the expansion of residual T cells and may be able to signal memory T cells to become productively infected without antigen recognition or overt stimulation and detectable proliferation⁵. For studies of DCs it is therefore critical to remove contaminating cells that may interact with the DCs, particularly when long term culture and p24 assays are used.