Monocyte-derived cultured dendritic cells are susceptible to human immunodeficiency virus infection and transmit virus to resting T cells in the process of nominal antigen presentation (original) (raw)
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Journal of Virology, 2007
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Blood, 1996
CD1a+ dendritic cells (DC) differentiate from a major population of nonadherent CD13(hi)lin- cells that appear when human cord blood CD34+ hematopoietic progenitor cells are cultured with stem-cell factor, granulocyte/macrophage (MA) colony-stimulating factor, and tumor necrosis factor-alpha (TNF-alpha) for 5 days. CD13hilin- cells, which also comprise MA and granulocyte precursors, are CD4+ and can thus be targets of human immunodeficiency virus (HIV). Low replication was noted when these day 5 cells were infected with lymphotropic HIV-1LA1 (p24: < or = 4 ng/mL on day 8 postinfection [PI]), while high virus production occurred with MA-tropic HIV-1Ba-L, HIV-1Ada, or HIV-1-m-n. (p24: 50 to > or = 1,000 ng/mL). Strong cytopathicity (CPE) was then observed in nonadherent cells as in adherent MA. However, FACS analysis on day 7 PI showed that HIV did not affect differentiation of DC that survived CPE: apart from CD4 downmodulation related to HIV production, overall expression of C...
HIV Induces Maturation of Monocyte-Derived Dendritic Cells and Langerhans Cells
The Journal of Immunology, 2006
In HIV infection, dendritic cells (DCs) may play multiple roles, probably including initial HIV uptake in the anogenital mucosa, transport to lymph nodes, and subsequent transfer to T cells. The effects of HIV-1 on DC maturation are controversial, with several recent conflicting reports in the literature. In this study, microarray studies, confirmed by real-time PCR, demonstrated that the genes encoding DC surface maturation markers were among the most differentially expressed in monocyte-derived dendritic cells (MDDCs), derived from human blood, treated with live or aldrithriol-2-inactivated HIV-1 BaL . These effects translated to enhanced cell surface expression of these proteins but differential expression of maturation markers was only partial compared with the effects of a conventional potent maturation stimulus. Such partially mature MDDCs can be converted to fully mature cells by this same potent stimulus. Furthermore, live HIV-1 stimulated greater changes in maturation marker surface expression than aldrithriol-2-inactivated HIV-1 and this enhanced stimulation by live HIV-1 was mediated via CCR5, thus suggesting both viral replication-dependent and -independent mechanisms. These partially mature MDDCs demonstrated enhanced CCR7-mediated migration and are also able to stimulate interacting T cells in a MLR, suggesting DCs harboring HIV-1 might prepare CD4 lymphocytes for transfer of HIV-1. Increased maturation marker surface expression was also demonstrated in native DCs, ex vivo Langerhans cells derived from human skin. Thus, HIV initiates maturation of DCs which could facilitate subsequent enhanced transfer to T cells.
Immunobiology of dendritic cells and the influence of HIV infection
Advances in experimental medicine and biology, 2013
Recent progress in phenotyping of human dendritic cells (DCs) has allowed a closer alignment of the classification and functions of murine and human dendritic cell subsets. Marked differences in the functions of these human DC subsets and their response to HIV infection have become apparent, relevant to HIV pathogenesis and vaccine and microbicide development. Systems biology approaches to studying HIV uptake and infection of dendritic cells has revealed how markedly HIV subverts their functions, especially in relation to the trafficking pathways and viral transfer to T cells. Furthermore the interactions between DCs and other innate immune cells, NK cells, NKT cells and gamma delta T cells are now known to influence DC and T cell function and are also disturbed by HIV infection in vitro and in vivo. Such cellular interactions are potential targets for vaccine adjuvants and immunotherapy.
Effect of HIV on antigen presentation by dendritic cells and macrophages
Research in virology
The antigen-presenting function of dendritic cells (DC) and macrophages (MO) following infection with HIV in vitro was examined. Using non-infected cells, DC, but not MO, stimulated primary proliferative responses in allogeneic lymphocytes in the mixed leukocyte reaction. Both DC and MO stimulated secondary responses to influenza virus and to tetanus toxoid in autologous T lymphocytes. After exposure of DC and MO to HIV1 in vitro for 2 days, 27% of DC but less than 1% MO became infected as assessed by in situ hybridization. DC were blocked in their capacity to stimulate responses to alloantigens or to the recall antigens. By contrast, MO retained the ability to stimulate responses to the recall antigens. Similar effects during in vivo infection would allow activated T-cell clones to respond to antigens presented by MO early in infection. However, any loss of activated T cells might prove cumulative and damaging in the absence of an effective DC recruitment mechanism for resting T ce...
Immunology
Dendritic cells (DC) have a potent antigen-presenting capacity for recruiting resting T cells into immune responses. They also promote expansion of already activated memory T cells. By contrast, macrophages (MO) are only effective in stimulating memory responses." 2 Infection and depletion of DC occur in human immunodeficiency virus (HIV)-infected individuals and recruitment of T cells into primary responses is blocked.3 Here comparisons between DC and MO in stimulating secondary T-cell responses in HIV infection were made. Adherent MO, and DC isolated by a new method, were separated from peripheral blood of patients in different stages of HIV infection and from uninfected controls and added to allogeneic lymphocytes in mixed leucocyte reactions (MLR). Some were pulsed with influenza virus or tetanus toxoid and used to stimulate autologous T cells. Responses were measured from uptake of [3H]thymidine in 20 pi hanging drop cultures. DC, but not MO, from normal individuals stimulated MLR but both populations stimulated secondary responses to recall antigens. DC from all HIV seropositive individuals caused little or no stimulation of any lymphocyte responses. However, MO from HIV seropositive asymptomatic individuals and those with persistent generalized lymphadenopathy stimulated responses to recall antigens. There was no stimulation using cells from acquired immune deficiency syndrome (AIDS) patients. Blocked DC but not MO function may underlie progressive immunological non-responsiveness in HIV infection. Without recruitment of resting T cells, loss of memory T cells4-6 may be cumulative; failure of secondary activation (e.g. by MO) would lead to lost T-cell activity. Identification and circumvention of the defect in DC could offer new therapeutic approaches.
The Journal of Immunology, 2002
Vaccination of cynomolgus monkeys with the biologically active HIV-1 Tat protein induces specific Th1 responses, including CTLs. Similar responses are also induced by vaccination with tat DNA, but not by vaccination with inactivated Tat or Tat peptides. This suggested that the native Tat protein may act differently on APC as compared with inactivated Tat or peptide Ag. In this study, we show that biologically active Tat is very efficiently taken up by monocyte-derived dendritic cells (MDDC) in a time (within minutes)- and dose-dependent (starting from 0.1 ng/ml) fashion, whereas uptake is very poor or absent with other APC, including T cell blasts and B lymphoblastoid cell lines. Although maturation of MDDC reduces their pino/phagocytic activity, mature MDDC take up Tat much more efficiently than immature cells. In addition, Tat uptake is abolished or greatly hampered by oxidation/inactivation of the protein or by performing the experiments at 4°C, suggesting that MDDC take up nativ...
Journal of General Virology, 1987
Preparations of human peripheral blood dendritic cells have been infected with human immunodeficiency virus (HIV). After 5 days in culture they were examined by electron microscopy. Virus was observed budding from the plasma membrane of dendritic cells and mature virions were observed on the cell surface. In addition, a second cell type, similar in morphology to 'classical' dendritic cells but containing numerous cytoplasmic granules, was also found to support replication of the virus. We speculate that the growth of HIV in dendritic cells could cause immunosuppression by impairing antigen presentation.
AIDS Research and Human Retroviruses, 2010
Monocytes serve as a systemic reservoir of myeloid precursors for the renewal of tissue macrophages and dendritic cells (DCs). Both monocytes and dendritic cells can be infected with HIV-1. Circulating DCs are believed to be derived from a common precursor of monocytes, or, in the case of inflammatory challenge, from monocytes directly. Because there are fewer infected blood monocytes than infected cells after differentiation, we hypothesized that the majority of HIV-1 infection in circulating DCs occurs via direct viral binding to their CD4 and coreceptors after differentiation. We isolated monocytes at one time point and circulating dendritic cells at a second time point from the blood of HIV-1-infected patients. Proviral DNA was isolated from DCs and monocytes, and the C2-V4 region of the HIV-1 env gene was cloned and sequenced. Phylogeny, nucleotide distances, and glycosylation patterns of the env gene were performed. The phylogenetic trees revealed that viral forms from the monocytes clustered distantly from the quasispecies derived from circulating DCs. The nucleotide distances and differing glycosylation patterns suggest that the infection of DCs is independent of the infection of the monocytes.