Characterization of the Cytotoxic Factor(s) Released from Thymic Dendritic Cells upon Human Immunodeficiency Virus Type 1 Infection

Beaulieu, Sylvie; Lafontaine, Marielle; Richer, Martin J.; Courchesne, Isabelle; Cohen, Éric A.; Bergeron, Dominique

doi:10.1006/viro.1997.8977

Cited by 18 publications

(18 citation statements)

References 58 publications

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“…In fact, HIV infection of human DC leads to release of an as yet unidentified soluble factor(s), which induces apoptosis of thymocytes and activated peripheral blood mononuclear cells. 68 TRAIL involvement in this killer activity has not been tested yet, but increased sensitivity of T cells from HIV patients to TRAIL-induced apoptosis has been described. 69,70 Cytotoxic activity of either measles virus-or HIV-infected DC results in lymphocyte apoptosis and may be TRAIL mediated.…”

Section: Discussionmentioning

confidence: 99%

Pathogenesis of Ebola Hemorrhagic Fever in Cynomolgus Macaques

Geisbert

Hensley

Larsen

et al. 2003

The American Journal of Pathology

531

327

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Ebola virus (EBOV) infection causes a severe and fatal hemorrhagic disease that in many ways appears to be similar in humans and nonhuman primates; however, little is known about the development of EBOV hemorrhagic fever. In the present study, 21 cynomolgus monkeys were experimentally infected with EBOV and examined sequentially over a 6-day period to investigate the pathological events of EBOV infection that lead to death. Importantly, dendritic cells in lymphoid tissues were identified as early and sus-

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Section: Discussionmentioning

confidence: 99%

Pathogenesis of Ebola Hemorrhagic Fever in Cynomolgus Macaques

Geisbert

Hensley

Larsen

et al. 2003

The American Journal of Pathology

531

327

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“…We hypothesize that virion production by CD4 ϩ T cells is efficient and rapid in the presence of HIV-infected LC and SEB, inducing apoptosis of infected T cells before significant proliferation can occur. HIV-infected LC may have produced pro-apoptotic factors in the presence of SEB, because HIV-infected APCs have previously been reported to produce pro-apoptotic factors, including TNF-␣ (20,21,25), Fas ligand (25), and TNF-related apoptosis-inducing ligand (26,27).…”

Section: Discussionmentioning

confidence: 99%

HIV-Infected Langerhans Cells Preferentially Transmit Virus to Proliferating Autologous CD4+ Memory T Cells Located within Langerhans Cell-T Cell Clusters

Sugaya

Loré

Koup

et al. 2004

The Journal of Immunology

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Langerhans cells (LC) are likely initial targets for HIV following sexual exposure to virus and provide an efficient means for HIV to gain access to lymph node T cells. The purpose of this study was to examine the nature of the CD4+ T cell that becomes infected by HIV-infected LC. We infected human LC within tissue explants ex vivo and then, 3 days later, cocultured HIV-infected LC with different subsets of autologous CD4+ T cells. Using multicolor flow cytometric analyses of LC-CD4+ T cell cocultures, we documented that HIV-infected LC preferentially infected memory (as compared with naive) CD4+ T cells. Proliferating and HIV-infected CD4+ memory T cells were more frequently detected in conjugates of LC and autologous CD4+ T cells, suggesting that T cells become activated and preferentially get infected through cluster formation with infected LC, rather than getting infected with free virus produced by single HIV-infected LC or T cells. p24+ Memory CD4+ T cells proliferated well in the absence of superantigen; by contrast, p24+ T cells did not divide or divided only once in the presence of staphylococcal enterotoxin B, suggesting that virus production was rapid and induced apoptosis in these cells before significant proliferation could occur. These results highlight that close interactions between dendritic cells, in this case epidermal LC, and T cells are important for optimal HIV replication within specific subsets of CD4+ T cells. Disrupting cluster formation between LC and memory CD4+ T cells may be a novel strategy to interfere with sexual transmission of HIV.

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“…Bergeron et al address the mechanism of thymocyte death by applying supernatants from infected thymic dendritic cells to purified CD4+ and CD8+ thymocytes and show that cell death ensues without accumulation of trypan blue positive cells, suggesting rapid decimation or engulfment [7,10]. Because cyclohexamide incubation inhibits this death, an active apoptotic process rather than passive necrosis is suggested.…”

Section: Mechanisms Of Thymocyte Death: Apoptosis Vs Necrosismentioning

confidence: 99%

HIV-1 Replication and Pathogenesis in the Human Thymus

Meissner¹,

Duus²,

Loomis³

et al. 2003

CHR

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How HIV replicates and causes destruction of the thymus, and how to restore thymic function, are among the most important questions of HIV-1 pathogenesis and therapy in adult as well as pediatric patients. The thymus appears to function, albeit at reduced levels, throughout the life of adults, to respond to T cell depletion induced by HIV and to be suppressed by HIV. In this review, we summarize recent findings concerning HIV replication and pathogenesis in the human thymus, focusing on mechanistic insights gleaned from studies in the SCID-hu Thy/Liv mouse and human fetal-thymus organ culture (HF-TOC) models. First, we discuss HIV viral determinants and host factors involved in the replication of HIV in the thymus. Second, we consider evidence that both viral factors and host factors contribute to HIV-induced thymocyte depletion. We thus propose that multiple mechanisms, including depletion and suppression of progenitor cells, paracrine and direct lytic depletion of thymocytes, and altered thymocyte selection are involved in HIV-induced pathology in the thymus. With the SCID-hu Thy/Liv mouse and HF-TOC models, it will be important in the coming years to further clarify the virological, cell biological, and immunological mechanisms of HIV replication and pathogenesis in human thymus, and to correlate their significance in HIV disease progression.

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Characterization of the Cytotoxic Factor(s) Released from Thymic Dendritic Cells upon Human Immunodeficiency Virus Type 1 Infection

Cited by 18 publications

References 58 publications

Pathogenesis of Ebola Hemorrhagic Fever in Cynomolgus Macaques

Pathogenesis of Ebola Hemorrhagic Fever in Cynomolgus Macaques

HIV-Infected Langerhans Cells Preferentially Transmit Virus to Proliferating Autologous CD4+ Memory T Cells Located within Langerhans Cell-T Cell Clusters

HIV-1 Replication and Pathogenesis in the Human Thymus

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