Analysis of human immunodeficiency virus type 1 (HIV-1) variants and levels of infection in dendritic and T cells from symptomatic HIV-1-infected patients.

Patterson, Steven; English, Nicholas R.; Longhurst, Hilary; Balfe, Peter; Helbert, Matthew; Pinching, Anthony J.; Knight, Stella C.

doi:10.1099/0022-1317-79-2-247

Cited by 34 publications

(25 citation statements)

References 61 publications

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“…Despite these caveats, our findings in transgenic mice are in agreement with some reports for HIV-positive individuals. Indeed, in some HIV-positive individuals, DC were not found to be decreased in the spleen (51), while their numbers were reported to be low in blood (10,20,21,25,33,38,49,57,59), skin (55), lymphoid tissue (47), and oral mucosa (80).…”

Section: Discussionmentioning

confidence: 99%

The AIDS-Like Disease of CD4C/Human Immunodeficiency Virus Transgenic Mice Is Associated with Accumulation of Immature CD11b^HiDendritic Cells

Poudrier

Weng

Kay

et al. 2003

J Virol

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CD4C/human immunodeficiency virus (HIV) transgenic mice develop an AIDS-like disease. We used this model to study the effects of HIV-1 on dendritic cells (DC). We found a progressive decrease in total DC numbers in the lymph nodes, with a significant accumulation of CD11bHi DC. In the thymus, the recovery of transgenic CD8␣؉ DC had a tendency to be lower. Spleen DC were augmented in the marginal zone. Transgenic DC showed a decreased capacity to present antigen in vitro, consistent with their reduced major histocompatibility complex class II expression and impaired maturation profile. The accumulation of immature DC may contribute to disease and may reflect an adaptive advantage for the virus by favoring its replication and preventing the generation of fully functional antiviral responses.Dendritic cells (DC) are involved in the generation of immune responses as well as in the selection and maintenance of the T-cell repertoire (3,46,54,75,78,81). During human immunodeficiency virus type 1 (HIV-1) infection, Langherans cells and DC at the mucosal surfaces are the earliest cell types to be exposed to HIV-1 in vivo and are thought to facilitate transmission of the virus to CD4 ϩ T cells following their migration to the lymph nodes (6, 64; reviewed in references 43, 71, and 86). HIV-1 is known to replicate preferentially in immature DC (32), and HIV-1 footprints have been detected in blood-, adenoid/tonsil-, and skin-derived DC from HIVpositive individuals (12,28,45,49,68), but not in all studies (5,40). This controversy about the extent of infection of human DC in vivo is also apparent regarding the effects of HIV-1 on DC differentiation, phenotype, and function, where a consensus has been difficult to reach, given the various sources of DC being studied, their stages of differentiation, their mode of isolation and culture, and the various stimuli used (7,43,86). It is therefore not clear whether and how HIV-1 affects DC populations and their function. Neither is it known whether "myeloid" and "plasmacytoid" DC subpopulations, the latter being most probably of lymphoid origin (79), are affected differently by HIV-1.To gain insight into the pathogenesis of HIV-1, we previously generated CD4C/HIV transgenic mice, which express HIV-1 gene products in CD4ϩ T cells and in cells of the macrophage/dendritic lineages and develop a severe AIDS-like disease. This disease is characterized by atrophy of the lymphoid organs and by gradual and preferential loss of CD4 ϩ T cells and of their functions (34, 35). These mice also exhibit an impaired capacity to generate germinal center reactions and harbor hyperresponsive B cells and serum autoantibody (65).Here we report our study on DC in these transgenic mice. MATERIALS AND METHODS Mice. The CD4C/HIVMutA transgenic mice have been described previously (35). Sex-matched littermates were used between 6 and 20 weeks of age. In order to generate in vitro mixed leukocyte reaction, CD4 ϩ lymphocytes from sexmatched BALB/c mice were used between 6 and 12 weeks of age. For in vitro antige...

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Section: Discussionmentioning

confidence: 99%

The AIDS-Like Disease of CD4C/Human Immunodeficiency Virus Transgenic Mice Is Associated with Accumulation of Immature CD11b^HiDendritic Cells

Poudrier

Weng

Kay

et al. 2003

J Virol

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“…[18][19][20][21] Similarly, there are conflicting reports regarding the ability of DCs from HIV-1-infected patients to stimulate T-lymphocyte proliferation. 18,[20][21][22] Some have found an impairment in DC function 18 while others showed no difference between the ability of DCs from HIV-infected patients and from controls to stimulate allogeneic T lymphocytes.…”

Section: Introductionmentioning

confidence: 99%

Dysfunction and infection of freshly isolated blood myeloid and plasmacytoid dendritic cells in patients infected with HIV-1

Donaghy

Gazzard

Gotch

et al. 2003

Blood

242

233

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Recently it has been shown that the 2 populations of blood dendritic cells (DCs), termed plasmacytoid (pcDCs) and myeloid (myDCs), are reduced in HIV-1 infection. This study aimed to determine whether these 2 populations are targets for HIV-1 infection and whether their ability to stimulate T-lymphocyte proliferation is affected. Highly purified populations of myDCs and pcDCs were isolated from the blood of antiretroviral treatmentnaive patients and assessed for the level of HIV provirus by polymerase chain reaction (PCR). We show that both populations are targets for HIV-1 infection as indicated by the presence of provirus in 12 of 14 pcDC and 13 of 14 myDC samples tested. A proportion of this provirus is integrated in myDCs. The ability of both myDCs and pcDCs from HIV-1-infected patients to stimulate allogeneic T-lymphocyte proliferation in a 6-day mixed leukocyte reaction was severely impaired, IntroductionPrimary adaptive immune responses are initiated by dendritic cells (DCs) through the presentation of antigen to T lymphocytes. DCs are also important stimulators of innate immune responses. 1,2 DCs constitute about 1% of the mononuclear cell population of blood and can be divided into 2 major subpopulations that are phenotypically and functionally distinct. 3,4 Myeloid DCs (myDCs) express CD11c, CD13, CD33, and the receptor for granulocyte-macrophage colony-stimulating factor (GM-CSF) and secrete interleukin 12 (IL-12). They are precursors of classical antigen-presenting cells, including Langerhans cells and dermal and interstitial DCs. 5 By contrast, plasmacytoid DCs (pcDCs) are CD11c Ϫ ; lack myeloid markers but express CD68, CD36, IL-3 receptor-␣ (IL-3R␣), immunoglobulin-like transcript 3 (ILT3); and produce high amounts of interferon-␣ (IFN-␣), 6,7 a potent inhibitor of HIV-1 replication. 8 Unlike myDCs, which migrate to the tissues and intercept invading pathogens before migrating to the lymph nodes, pcDCs migrate directly from blood to the secondary lymphoid tissue where they differentiate into cells originally termed plasmacytoid T cells on the basis of their extensive endoplasmic reticulum. 9,10 It has long been known that during HIV-1 infection there is a progressive decline in CD4 T-lymphocyte numbers, and in the later stages of disease there is loss of HIV-specific cytotoxic Tlymphocyte activity. 11 Recently, we and others have reported that there is also a progressive loss in the number of blood DCs. [12][13][14][15] However, to fully understand the role of DCs in the pathogenesis of HIV-1, it is important to determine whether the 2 DC populations are targets for HIV-1 infection and whether their ability to stimulate T lymphocytes in infected individuals is affected. Evidence of infection would be important as it would provide a mechanism to explain DC loss and might facilitate infection of T lymphocytes during antigen presentation. Down-regulation of T-lymphocyte stimulatory capacity together with reduced numbers would severely suppress cell-mediated immunity and contribute to the immunosuppr...

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“…11 Several studies found that DCs are susceptible to human immunodeficiency virus type 1 (HIV-1) infection in vitro, 12,13 findings that correlate with loss and infection of DCs in vivo. 14,15 However, how loss of DCs correlates with disease progression or whether there is loss in one or both populations of DCs is unknown. In this study, we observed a progressive loss of both myDC and pcDC populations with increasing HIV-1 virus load.…”

Section: Introductionmentioning

confidence: 99%

Loss of blood CD11c+ myeloid and CD11c−plasmacytoid dendritic cells in patients with HIV-1 infection correlates with HIV-1 RNA virus load

Donaghy

Pozniak

Gazzard

et al. 2001

Blood

359

274

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Human blood contains at least 2 subpopulations of antigen-presenting dendritic cells (DCs) that can be differentiated by their expression of CD11c. Myeloid DCs (myDCs), which are CD11c ؉ , trap invading pathogens in the tissues and then migrate to lymphoid tissues where they stimulate pathogenspecific T-cell responses. Plasmacytoid DCs (pcDCs), which are CD11c ؊ , secrete interferon-␣ in response to viral infections. This study reports that in HIV-1 infection there is a progressive depletion of both these DC populations and that this correlates with an increasing HIV-1 plasma virus load. The median numbers of myDCs and pcDCs were 6978/mL and 9299/mL, respectively, in healthy male controls and 2298/mL and 1640/mL, respectively, in patients with more than 10 5 HIV-1 RNA copies/mL. Both DC populations expressed CD4, CCR5, and CXCR4. The findings suggest that loss of DCs in HIV infection may contribute to disease progression.

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Analysis of human immunodeficiency virus type 1 (HIV-1) variants and levels of infection in dendritic and T cells from symptomatic HIV-1-infected patients.

Cited by 34 publications

References 61 publications

The AIDS-Like Disease of CD4C/Human Immunodeficiency Virus Transgenic Mice Is Associated with Accumulation of Immature CD11b^HiDendritic Cells

The AIDS-Like Disease of CD4C/Human Immunodeficiency Virus Transgenic Mice Is Associated with Accumulation of Immature CD11b^HiDendritic Cells

Dysfunction and infection of freshly isolated blood myeloid and plasmacytoid dendritic cells in patients infected with HIV-1

Loss of blood CD11c+ myeloid and CD11c−plasmacytoid dendritic cells in patients with HIV-1 infection correlates with HIV-1 RNA virus load

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Analysis of human immunodeficiency virus type 1 (HIV-1) variants and levels of infection in dendritic and T cells from symptomatic HIV-1-infected patients.

Cited by 34 publications

References 61 publications

The AIDS-Like Disease of CD4C/Human Immunodeficiency Virus Transgenic Mice Is Associated with Accumulation of Immature CD11bHiDendritic Cells

The AIDS-Like Disease of CD4C/Human Immunodeficiency Virus Transgenic Mice Is Associated with Accumulation of Immature CD11bHiDendritic Cells

Dysfunction and infection of freshly isolated blood myeloid and plasmacytoid dendritic cells in patients infected with HIV-1

Loss of blood CD11c+ myeloid and CD11c−plasmacytoid dendritic cells in patients with HIV-1 infection correlates with HIV-1 RNA virus load

Contact Info

Product

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The AIDS-Like Disease of CD4C/Human Immunodeficiency Virus Transgenic Mice Is Associated with Accumulation of Immature CD11b^HiDendritic Cells

The AIDS-Like Disease of CD4C/Human Immunodeficiency Virus Transgenic Mice Is Associated with Accumulation of Immature CD11b^HiDendritic Cells