Immunodeficiency virus uptake, turnover, and 2-phase transfer in human dendritic cells

Turville, Stuart; Santos, John J.; Frank, Ines; Cameron, Paul; Wilkinson, John; Miranda-Saksena, Monica; Dable, Joanne; Stössel, Hella; Romani, Nikolaus; Piatak, Michael; Lifson, Jeffrey D.; Pope, Melissa; Cunningham, Anthony L.

doi:10.1182/blood-2003-09-3129

Cited by 369 publications

(595 citation statements)

References 51 publications

(100 reference statements)

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“…[17][18][19] Recent studies have indicated that HIV-1 may be more effectively transmitted during antigen presentation between CD4 + T cells and HIV-1 exposed or infected dendritic cells (DCs), termed an infectious immunological synapse, thus providing a means for increased local viral levels. [20][21][22][23][24] As it may be impossible to protect all susceptible cells in an individual through gene delivery, the delivered protection must function to allow a limited number of primary T cells to survive, enrich, and function in the face of a robust, widespread HIV-1 infection mediated via free virus and cell-to-cell interaction.…”

Section: Introductionmentioning

confidence: 99%

T-cell protection and enrichment through lentiviral CCR5 intrabody gene delivery

et al. 2006

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CCR5 is the chemokine co-receptor for R5-tropic human immunodeficiency virus type 1 (HIV-1) isolates most often associated with primary infection. We have developed an HIV-1 self-inactivating vector, CAD-R5, containing a CCR5 single-chain antibody (intrabody) gene, which when expressed in T-cell lines and primary CD4 + T cells disrupts CCR5 cell surface expression and provides protection from R5-tropic isolate exposure. Furthermore, CAD-R5 intrabody expression in primary CD4 + T cells supports significant growth and enrichment over time during HIV-1-pulsed dendritic cell-T-cell interactions. These results indicate that CCR5 intrabody-expressing CD4 + T cells are refractory against this highly efficient primary route of infection. CD34 + cells transduced with the CAD-R5 vector gave rise to CD4 + and CD8 + thymocytes in non-obese diabetic (NOD)/ severely combined-immunodeficient (SCID)-human thymus/ liver (hu thy/liv) mice, suggesting that CCR5 intrabody expression can be maintained throughout differentiation without obvious cellular effects. CD4 + T cells isolated from NOD/SCID-hu thy/liv mice were resistant to R5-tropic HIV-1 challenge demonstrating the maintenance of protection. Our findings demonstrate delivery of anti-HIV-1 activity through CCR5 intrabodies in primary CD4 + T cells and CD34 + cell-derived T-cell progeny. Thus, gene delivery strategies that provide a selective survival and growth advantage for T effector cells may provide a therapeutic benefit for HIV-1-infected individuals who have failed conventional therapies.

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Section: Introductionmentioning

confidence: 99%

T-cell protection and enrichment through lentiviral CCR5 intrabody gene delivery

et al. 2006

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“…Langerhans Cells (LC), which are a subtype of DC found in tissues, have increased HIV uptake after stimulation [63]. This could parallel stimulation of DC by BV CVL samples leading to an increase in the macropinocytosis of virions [64].…”

Section: Discussionmentioning

confidence: 99%

Dendritic cell activation and maturation induced by mucosal fluid from women with bacterial vaginosis

John

Martinson

Simões

et al. 2007

Clinical Immunology

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Dendritic cells (DC) at mucosal surfaces mature when exposed to "danger" signals such as LPS. Bacterial vaginosis (BV) is a prevalent alteration of the vaginal bacterial flora associated with preterm childbirth and increased risk for HIV acquisition. We examined the effect of mucosal fluid from women with BV or healthy flora on DC function. IL-12, IL-23 and p40 production by monocytederived dendritic cells (MDDC) were all induced by BV samples. Activation/maturation markers HLA-DR, CD40, and CD83 on MDDC incubated with BV CVL were also induced. BV CVL also decreased the endocytic ability of MDDC and increased proliferation of T-cells in allogeneic MLR. Plasmacytoid dendritic cell (pDC) CD86 expression was induced by BV CVL. Healthy flora CVL had little effect in any of the tests. This study suggests that BV, but not healthy flora, affects local dendritic cell function in vivo suggesting a mechanism through which BV affects mucosal immunity.

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Section: Subsets In Hiv-1 Transmissionmentioning

confidence: 99%

“…HIV-containing endosomes are diverted to the contact region, fuse with the cell membrane dumping their load of residual HIV into the synapse. Thus the amount of virus transferred declines over 12 h because of the endocytic degradation [28]. Conversely transfer of de novo produced virus which is also diverted to the contact region and in filopodia surrounding CD4 lymphocytes increases over 24-72 h [33].…”

Section: Subsets In Hiv-1 Transmissionmentioning

confidence: 99%

“…These data imply that immature DC and LC in contrast to their mature forms are more important in HIV-1 transmission. Viral endocytosis leads to partial acid-proteolytic degradation in the late endosome, although some virus may be retained in its infectious state for longer periods [27,28] [26]. However, HIV entry via fusion leads to de novo productive infection first detectable at 24 h and with a plateau in vitro at 72 h. Recent studies suggest this de novo produced virus can re-enter the same or adjacent DC by endocytosis and the latter can also be infected de novo, thus mixing up the initial two distinct phases of viral endocytic degradation and de novo infection.…”

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Langerhans cells and viral immunity

2008

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Langerhans cells (LC) are a unique dendritic cell subset that are located in mucosal stratified squamous epithelium and skin epidermis. Their location is ideally suited for their function as antigen presenting cells that capture invading viruses and induce anti-viral immunity. However, it is becoming evident that the interaction between LC and viruses can result in different responses, depending on the virus and the receptors involved. Here we will discuss the recent data on the similarities and differences in roles of LC in viral immunity to and infection with HIV, herpes simplex and varicella-zoster virus. Although all three viruses interact with LC during initial infection, the effects can be quite different, reflecting differences in biology and pathogenesis. Key words: Dendritic cells Á Langerhans cells Á Infectious diseases Á HIV Á HerpesvirusesSee accompanying mini-review by Kaplan et al. Biology of LC and interactions with virusesThe resident epidermal dendritic cells (DC), Langerhans cells (LC), form a tight network with each other and with the surrounding keratinocytes via E-cadherin in the skin or mucosal stratified squamous epithelium. In the anogenital region they are distributed throughout the anogenital skin and mucosa including vagina, ectocervix as well as male foreskin. In stratified squamous epithelium, LC overlie interstitial or dermal DC [1]. LC can repopulate from local and blood-borne precursors (reviewed by Kaplan et al. in this issue [2]). Similar to other myeloid DC, LC are able to bridge innate and adaptive immunity. They are able to interact directly with microorganisms at the periphery to produce effector cytokines and initiate or restimulate activation of T and B lymphocytes through antigen presentation. LC express different pattern recognition receptors such as C-type lectin receptors (CLR) and Toll-like receptors (TLR), to bind and capture pathogens. These interactions result in activation of intracellular signalling pathways leading to LC activation and cytokine induction. The CLR expressed by skin DC differ by site: Langerin by epidermal LC and DC-SIGN and mannose receptor by dermal DC. LC like other migratory DC are in an immature, highly endocytic state while sessile in the skin/mucosa. However after pathogen binding to TLR and uptake, LC become mature and migratory, downregulating their endocytic and antigen processing capacity. Mature LC migrate to the lymph nodes where they are directly or indirectly involved in presentation of pathogenderived antigens on MHC Class I and II to T cells, resulting in activation of antigen-specific T cells [2][3][4]. Recent studies have raised the possibility that LC may have an immunosuppressive role [5][6][7]. Kaplan et al. [2] showed that contact hypersensitivity was amplified on LC ablation, while Cumberbatch et al.[5] found defective LC mobilisation in patients with psoriasis. Immunosuppression rather than stimulation could be explained, in part, by the maturational process associated with LC migration during steady-state conditions. Jian...

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Immunodeficiency virus uptake, turnover, and 2-phase transfer in human dendritic cells

Cited by 369 publications

References 51 publications

T-cell protection and enrichment through lentiviral CCR5 intrabody gene delivery

T-cell protection and enrichment through lentiviral CCR5 intrabody gene delivery

Dendritic cell activation and maturation induced by mucosal fluid from women with bacterial vaginosis

Langerhans cells and viral immunity

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