Dendritic Cell-T Cell Mixtures, Isolated from the Skin and Mucosae of Macaques, Support the Replication of SIV

Abstract

Previous studies have shown that HIV-1 exploits dendritic cells (DCs) to replicate and spread among CD4+ T cells. The DCs within mucosal surfaces may be especially important, but these are more difficult to access. To study more extensively the properties of DCs and other leukocytes from skin and different mucosae, DCs were isolated from uninfected macaques and their sensitivity assessed to infection with SIV in vitro. Dendritic cells and T cells readily emigrated from organ cultures of macaque skin, as described previously for humans. In addition, characteristic cells emigrated from explants of mucosae, both nasopharyngeal (adenoid and tonsil) and genital (vagina and cervix). The macaque DCs reacted with the monoclonals that are used to study human DCs, such as MAbs to CD40, CD86, CD83, and the p55 protein. When SIV was added to the DC-T cell mixtures from these different organs, extensive replication was observed in all but the cervical leukocytes. SIV replication occurred without the use mitogens, and with virus that had been grown in a cell line in the absence of mitogens and IL-2. Most of the newly synthesized viral protein is observed in syncytia. Therefore, mixtures of DCs and T cells isolated from mucosal surfaces served as a naturally permissive environment for SIV replication.

CpG-C Immunostimulatory Oligodeoxyribonucleotide Activation of Plasmacytoid Dendritic Cells in Rhesus Macaques to Augment the Activation of IFN-γ-Secreting Simian Immunodeficiency Virus-Specific T Cells

“…Macaque and human DCs exhibit comparable biology (42)(43)(44)(45), with more recent work confirming the presence of MDCs and PDCs in circulation (46 -48). Aldrithiol-2 (AT-2)-inactivated SIV that is noninfectious yet retains functional surface proteins, interacts authentically with DCs (49,50), making it a useful tool to monitor the presentation of DC-captured virions for immune stimulation (44,51); similar results have been obtained in vitro with AT-2 HIV and human DCs (52,53).…”

Endogenously Expressed nef Uncouples Cytokine and Chemokine Production from Membrane Phenotypic Maturation in Dendritic Cells

“…The cloned viruses SIVmac239 (wild type) and SIVmac239 delta nef (delta nef) (36) were grown as previously described (37).…”

The Maturation of Dendritic Cells Results in Postintegration Inhibition of HIV-1 Replication

“…There is evidence that Langerhans cells (LC) from genital or rectal epithelia are among the first targets of HIV (2-4), and could be responsible for both virus transport to draining lymph nodes (5) and preferential transmission of CCR5-dependent R5 strains (6 -8). DC from lymphoid tissues (e.g., tonsils, adenoids, lymph nodes, Peyer's patches) of chronically infected subjects are frequently involved in p55 ϩ S100 ϩ CD68 ϩ multinucleated giant cells (9 -12) or closely associated with HIV-or SIV-infected T lymphocytes (13)(14)(15)(16)(17), while LC from the cervix and vaginal lamina propria could represent a virus reservoir in vivo (18). Accordingly, DC and LC isolated from the blood, the skin, or genital tract, or differentiated in vitro from CD34 ϩ hemopoietic progenitor cells (HPC) or from monocytes, express CD4 and HIV coreceptors, CCR5 and CXCR4, and are permissive to HIV (8, 19 -33).…”